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BACKGROUND: Langerhans cell histiocytosis belongs to a group of diseases of of the monocyte system. In 2016 was reclassified into 5 groups, this one belongs to group L, with participation of gain-of-function in the mitogen-activated protein kinase signal transduction pathway (MAPK). CLINICAL CASE: male in the seventh decade of life diagnosed with diabetes insipidus. He begins with an erythematous, ulcerated plaque, with serohematic exudate in the right groin, followed by lesions of the same characteristics in the bilateral atriocephalic groove and perianal skin. The histopathological study evidenced a proliferation of immunoreactive histiocytic cells for protein S-100, CD68, CD1a and Langerin with a diagnosis of Langerhans cell histiocytosis. CONCLUSIONS: Langerhans cell histiocytosis can present unusual cutaneous manifestations, so taking a biopsy for histopathological and immunohistochemical study are essential for proper classification. [ABSTRACT FROM AUTHOR]

Indeterminate dendritic cell tumor (IDCT) is rare histiocytic tumor characterized by the proliferation of indeterminate dendritic cells. It is more often diagnosed in middle-aged people, in approximately equal proportions in men and women. The etiology of IDCT is unknown. Differential diagnosis is carried out with other diseases that mimic IDCT and is important for determining treatment tactics. The present paper presents a clinical case of IDCT in a 48-year-old man. The similarity of skin manifestations in IDCT with other cutaneous pathologies requires an immunohistochemical study of the affected areas for CD1a, CD68, S100, Langerin expression evaluation as well as the presence of Birbeck's granules visualization. Routine histological examination does not sufficient for correct IDCT diagnostics.

Langerhans cell histiocytosis (LCH) is a rare neoplastic disease characterized by abnormal proliferation of Langerhans cells infiltrating various organs, resulting in organ dysfunction. In some patients, the BRAFV600E mutation can be detected. Histopathology reveals a substantial proliferation of Langerhans cells, contributing significantly to the diagnosis of LCH. Clinical manifestations vary depending on the affected tissues or organs. LCH occurs less frequently in adults than in children, and clinicians often lack sufficient awareness of this disease, making it susceptible to misdiagnosis. In this report, a case of liver injury caused by Langerhans cell invasion is presented, as confirmed by a liver biopsy in adults.

Background: Langerhans cell histiocytosis (LCH) has heterogeneous presentations involving single or multiple systems, but simultaneous isolated skin and gastrointestinal involvement is not common. Case report: A female infant with intermittent bloody diarrhea was unresponsive for treatment of food allergy. Histology of gastric and colonic tissues demonstrated Langerhan's cell histiocytosis. The infant also had red rashes that were histologically proven Langerhan's cell histiocytosis. Chemotherapy utilized vincristine, cytarabine and prednisone. The bloody diarrhea and rash completely resolved with no recurrence in the 11 months of follow-up. Conclusion: Langerhan cell histiocytosis may present with simultaneous gastrointestinal and skin involvement. [ABSTRACT FROM AUTHOR]

In this study, we investigated whether stimulating the skin with ultrasound (US) could activate Langerhans cells (LCs) – antigen-presenting cells in the epidermis and stimulate antibody production following the subcutaneous and intradermal injection of ovalbumin (OVA) in hairless rats and BALB/c mice. Three different US frequencies (20 kHz, 1, and 3 MHz) were used and the expression of langerin was monitored as a marker for the activation of LCs in the epidermal sheet. In hairless rats, the langerin signal peaked at 12 h post-US treatment and returned to control levels at 24 h. Its expression increased with increasing irradiation time, up to 20 min, and 20 kHz US induced the highest langerin expression among the three frequencies tested. These results were reproduced in BALB/c mice. When the skin was pretreated with 20 kHz US at 0.41 W/cm2 for 10 min, the production of OVA-specific immunoglobulin G1 in mice increased by 2.8- and 3.4-fold 28 days after subcutaneous or intradermal OVA injections, respectively. These findings indicate that stimulating the skin with US can trigger skin immune responses, leading to effective antigen-specific antibody production. US-assisted transdermal vaccine delivery delivers antigens to the skin and evokes an immune response, providing an effective noninvasive immunization strategy.

Introduction: Oral Squamous Cell Carcinoma (OSCC) accounts for about 2/3rd of the Head and Neck Squamous Cell Carcinomas (HNSCC). It is the sixth most common cancer worldwide and the third most common cancer in developing countries including India. More than half the HNSCC patients have advanced disease at the time of diagnosis and overall long-term survival is low (50%), despite aggressive therapeutic regimens. This has demanded the need for prognostic indicators that can be used to improve the ability to select a more individualised approach for treatment relative to the risks of recurrence, metastases and death. Aim: To study the intratumoural and peritumoural distribution and density of Langerhans Cells (LC) in OSCC using Immunohistochemistry (IHC) markers Cluster of Differentiation- 1a (CD1a) and Langerin and to study its association with known prognostic factors. Materials and Methods: This was a hospital-based crosssectional study conducted at the Department of Pathology, Amala institute of Medical Sciences, Kerala, India during a period of 18 months, from January 2019 to June 2020. In total, 28 specimens of wide local excision with cervical lymph node dissection done for OSCC were enrolled in the study. Small biopsy samples and cases who had undergone neoadjuvant treatment as well as cases of recurrent OSCC were excluded. Clinical details were obtained from the patients' case files. The immunohistochemical staining for LCs using CD1a and Langerin was done. The distribution of LCs was compared to the tumour grade and lymph node status along with lymphovascular and perineural invasion. Statistical analysis was performed using sample t-test after identifying normality of distribution. The p-value of <0.05 was taken as significant. Results: Fourteen cases of well differentiated and 14 cases of moderate to poorly differentiated OSCC were selected for the study. The LC distribution in these cases were compared to prognostic factors like histological grade, Lymphovascular Invasion (LVI), perineural invasion, tumour size, depth of invasion, T stage and lymph node status. A significant positive association was observed between the tumour differentiation and peritumoural CD1a positive cell density (p-value: 0.001). Further, a negative association was also established between the lymph node staging and peritumoural CD1a positive cell density (p-value: 0.004). There was no association between the LC density and presence of lymphovascular or perineural invasion in OSCC. Conclusion: A depleted peritumoural LC density in OSCC reflects poor tumour immunity, associated with higher grade and higher stage of lymph node metastasis. LC density may hence be of prognostic value in OSCC. [ABSTRACT FROM AUTHOR]

Introduction: Oral Squamous Cell Carcinoma (OSCC) accounts for about 2/3rd of the Head and Neck Squamous Cell Carcinomas (HNSCC). It is the sixth most common cancer worldwide and the third most common cancer in developing countries including India. More than half the HNSCC patients have advanced disease at the time of diagnosis and overall long-term survival is low (50%), despite aggressive therapeutic regimens. This has demanded the need for prognostic indicators that can be used to improve the ability to select a more individualised approach for treatment relative to the risks of recurrence, metastases and death. Aim: To study the intratumoural and peritumoural distribution and density of Langerhans Cells (LC) in OSCC using Immunohistochemistry (IHC) markers Cluster of Differentiation-1a (CD1a) and Langerin and to study its association with known prognostic factors. Materials and Methods: This was a hospital-based cross-sectional study conducted at the Department of Pathology, Amala institute of Medical Sciences, Kerala, India during a period of 18 months, from January 2019 to June 2020. In total, 28 specimens of wide local excision with cervical lymph node dissection done for OSCC were enrolled in the study. Small biopsy samples and cases who had undergone neoadjuvant treatment as well as cases of recurrent OSCC were excluded. Clinical details were obtained from the patients’ case files. The immunohistochemical staining for LCs using CD1a and Langerin was done. The distribution of LCs was compared to the tumour grade and lymph node status along with lymphovascular and perineural invasion. Statistical analysis was performed using sample t-test after identifying normality of distribution. The p-value of

Omenn syndrome, a rare form of combined immunodeficiency in infants, presenting with recurrent infections, erythroderma, lymphadenopathy, hepatosplenomegaly, eosinophilia, and increased serum IgE levels. It is a fatal condition unless treated by hematopoietic stem cell transplant. Hence, an early diagnosis and a prompt treatment can lead to better outcome in these unfortunate babies afflicted with Omenn syndrome. Here, we present an 8-week-old infant with typical features of Omenn syndrome, both clinically as well as on laboratory analysis, but surprising immunohistochemical findings on lymph node biopsy. [ABSTRACT FROM AUTHOR]

Human milk oligosaccharides (HMOs) and their most abundant component, 2′-Fucosyllactose (2′-FL), are known to be immunomodulatory. Previously, it was shown that HMOs and 2′-FL bind to the C-type lectin receptor DC-SIGN. Here we show, using a ligand-receptor competition assay, that a whole mixture of HMOs from pooled human milk (HMOS) and 2′-FL inhibit the binding of the carbohydrate-binding receptor DC-SIGN to its prototypical ligands, fucose and the oligosaccharide Lewis-B, (Leb) in a dose-dependent way. Interestingly, such inhibition by HMOS and 2′-FL was not detected for another C-type lectin, langerin, which is evolutionarily similar to DC-SIGN. The cell-ligand competition assay using DC-SIGN expressing cells confirmed that 2′-FL inhibits the binding of DC-SIGN to Leb. Molecular dynamic (MD) simulations show that 2′-FL exists in a preorganized bioactive conformation before binding to DC-SIGN and this conformation is retained after binding to DC-SIGN. Leb has more flexible conformations and utilizes two binding modes, which operate one at a time via its two fucoses to bind to DC-SIGN. Our hypothesis is that 2′-FL may have a reduced entropic penalty due to its preorganized state, compared to Leb, and it has a lower binding enthalpy, suggesting a better binding to DC-SIGN. Thus, due to the better binding to DC-SIGN, 2′-FL may replace Leb from its binding pocket in DC-SIGN. The MD simulations also showed that 2′-FL does not bind to langerin. Our studies confirm 2′-FL as a specific ligand for DC-SIGN and suggest that 2′-FL can replace other DC-SIGN ligands from its binding pocket during the ligand-receptor interactions in possible immunomodulatory processes. [ABSTRACT FROM AUTHOR]

Usutu virus (USUV) and West Nile virus (WNV) are phylogenetically close emerging arboviruses transmitted by mosquitoes, and constitute a global public health threat. Since USUV and WNV enter the body through the skin, the first immune cells they encounter are skin-resident dendritic cells, the most peripheral outpost of immune defense. This unique network is composed of Langerhans cells (LCs) and dermal DCs, which reside in the epidermis and the dermis, respectively. Using human skin explants, we show that while both viruses can replicate in keratinocytes, they can also infect resident DCs with distinct tropism, since WNV preferentially infects DCs in the dermis, whereas USUV has a greater propensity to infect LCs. Using both purified human epidermal LCs (eLCs) and monocyte derived LCs (MoLCs), we confirm that LCs sustain a faster and more efficient replication of USUV compared with WNV and that this correlates with a more intense innate immune response to USUV compared with WNV. Next, we show that ectopic expression of the LC-specific C-type lectin receptor (CLR), langerin, in HEK293T cells allows WNV and USUV to bind and enter, but supports the subsequent replication of USUV only. Conversely, blocking or silencing langerin in MoLCs or eLCs made them resistant to USUV infection, thus demonstrating that USUV uses langerin to enter and replicate in LCs. Altogether, our results demonstrate that LCs constitute privileged target cells for USUV in human skin, because langerin favors its entry and replication. Intriguingly, this suggests that USUV efficiently escapes the antiviral functions of langerin, which normally safeguards LCs from most viral infections.

Langerhans cell histiocytosis is mainly diagnosed in children, and its manifestation in adult age is quite uncommon. Skin rashes may be non-specific and mimic a number of dermatoses. Therefore, the clinical diagnosis is challenging and as a rule, such patients are misinterpreted and managed for other disorders by a dermatologist for some years. We present a clinical case of Langerhans cell histiocytosis with skin involvement in a 35-year female patient, who had been treated by a dermatologist for 2 years for pyoderma, seborrheic dermatitis, and skin fold candidiasis. Taking into account the clinical signs and symptoms and age of manifestation, we initially suspected familial benign pemphigus (Hailey-Hailey disease) or follicular dyskeratosis (Darier's disease). However, the histological assessment showed Langerhans cell histiocytosis confirmed by immunohistochemistry with anti-langerin, anti-CD1a, and anti-protein S-100 antibodies. The patient was referred to a hematologist for further work-upand specific treatment. In cases of any treatment resistant disorders, which do not respond to long-term conventional treatment, it is necessary to reconsider the diagnosis by means of histological investigation. It would allow for identification of a disease, which is uncommon in dermatology practice.

Human skin is a preferred vaccination site as it harbors multiple dendritic cell (DC) subsets, which display distinct C‐type lectin receptors (CLR) that recognize pathogens. Antigens can be delivered to CLR by antibodies or ligands to boost antigen‐specific immune responses. This concept has been established in mouse models but detailed insights into the functional consequences of antigen delivery to human skin DC in situ are sparse. In this study, we cloned and produced an anti‐human Langerin antibody conjugated to the EBV nuclear antigen 1 (EBNA1). We confirmed specific binding of anti‐Langerin‐EBNA1 to Langerhans cells (LC). This novel LC‐based vaccine was then compared to an existing anti‐DEC‐205‐EBNA1 fusion protein by loading LC in epidermal cell suspensions before coculturing them with autologous T cells. After restimulation with EBNA1‐peptides, we detected elevated levels of IFN‐γ‐ and TNF‐α‐positive CD4+ T cells with both vaccines. When we injected the fusion proteins intradermally into human skin explants, emigrated skin DC targeted via DEC‐205‐induced cytokine production by T cells, whereas the Langerin‐based vaccine failed to do so. In summary, we demonstrate that antibody‐targeting approaches via the skin are promising vaccination strategies, however, further optimizations of vaccines are required to induce potent immune responses. [ABSTRACT FROM AUTHOR]

Dendritic cells form the link between the innate and adaptative immune response, particularly on mucosal and epidermal surfaces. The Langerhans, an epidermal dendritic cell subpopulation, play a key role in the skin immune response across several species. Scarse immune cell subpopulations, including Langerhans-like cells, have been identified in endangered green turtles thereby complicating the understanding of the pathogenesis of diseases such as fibropapillomatosis, which induces skin tumours in this species worldwide. In biopsies from green turtle skin, we demonstrated that the polyclonal anti-human Langerin antibodies strongly stained a Langerin+ cell population in epidermal sheets, the suprabasal layer of the epidermis in cryosections and in cells from cytospin preparation of migration assays. The morphology of these cells was round to amoeboid in normal skin; however, in skin with ulcerative dermatitis, Langerin+ cells aggregated around ulcers and adopted a more pleomorphic morphology. To our knowledge, this is the first identification of Langerin+ cells with a molecular marker in a reptile species. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are “frontline” immune cells dedicated to antigen presentation. They serve as an important bridge connecting innate and adaptive immunity, and express various receptors for antigen capture. DCs are divided into various subclasses according to their differential expression of cell surface receptors and different subclasses of DCs exhibit specific immunological characteristics. Exploring the common features of each sub-category has became the focus of many studies. There are certain amounts of DCs expressing langerin in airways and peripheral lungs while the precise mechanism by which langerin+ DCs drive pulmonary disease is unclear. Langerin-expressing DCs can be further subdivided into numerous subtypes based on the co-expressed receptors, but here, we identify commonalities across these subtypes that point to the major role of langerin. Better understanding is required to clarify key disease pathways and determine potential new therapeutic approaches.

Multivalent ligands of the C‐type lectin receptor DC‐SIGN have emerged as effective antiadhesive agents against various pathogens. Some years ago, we described a hexavalent DC‐SIGN ligand, Polyman‐26, designed to bridge two of the four binding sites displayed by the receptor. In this work, we present our efforts to accomplish simultaneous coordination of all four carbohydrate binding sites of DC‐SIGN through the synthesis of cross‐shaped glycodendrimers. The tailored rigid scaffold allowed multivalent presentation of glycomimetics in a spatially defined fashion, while providing good water solubility to the constructs. Evaluation of the biological activity by SPR assays revealed strong binding avidity towards DC‐SIGN and increased selectivity over langerin. Inhibition of DC‐SIGN binding to SARS‐CoV‐2 spike protein and of DC‐SIGN mediated Ebola virus trans‐infection testifies for the glycodendrimers potential application in infection diseases. The tetravalent platform described here is easily accessible and can be used in modular fashion with different ligands, thus lending itself to multiple applications. [ABSTRACT FROM AUTHOR]

Background: Langerhans cell histiocytosis (LCH) is a rare malignant disorder of epidermal antigen presenting cells. It is characterized by infiltration of various tissues with dendritic cells (Langerhans cells, LC) that express CD1a or CD207 (langerin), often leading to organ dysfunction. A patient with LCH required liver transplantation (LT) for LCH-associated biliary-tract disease. Cholangiopathy developed after LT. The question arose: In this patient, did LC in damaged liver-allograft biliary epithelium signify acute cellular rejection (ACR) or recurrent LCH?, Methods: We evaluated immunohistochemical identification of LC (CD1a, CD207) in the proposita and in 14 ACR patient samples as distinguishing between ACR and recurrent LCH., Results: Among 15 patient samples, 3 (20%) marked with neither antibody. Among the remaining 12 samples (80%), 4 (26.7%)-including that from the proposita-had cells marking for both antigens within bile-duct epithelium as well as in surrounding portal-tract connective tissue, 2 (13.3%) had cells marking for both antigens in one region or the other, but not in both, and 6 (40%) had cells marking for only one antigen in one region or the other., Conclusions: Immunostaining for CD1a and CD207/langerin in the setting of ACR without suspicion of LCH identifies LC in damaged bile ducts. This biomarker pairing proved not to be LCH-specific. Our findings indicate that the presence of these cells alone is insufficient to identify recurrent LCH in the allograft liver., (© 2024 The Author(s). Pediatric Transplantation published by Wiley Periodicals LLC.)

Immune modulating therapies and vaccines are in high demand, not least to the recent global spread of SARS-CoV2. To achieve efficient activation of the immune system, professional antigen presenting cells have proven to be key coordinators of such responses. Especially targeted approaches, actively directing antigens to specialized dendritic cells, promise to be more effective and accompanied by reduced payload due to less off-target effects. Although antibody and glycan-based targeting of receptors on dendritic cells have been employed, these are often expensive and time-consuming to manufacture or lack sufficient specificity. Thus, we applied a small-molecule ligand that specifically binds Langerin, a hallmark receptor on Langerhans cells, conjugated to a model protein antigen. Via microneedle injection, this construct was intradermally administered into intact human skin explants, selectively loading Langerhans cells in the epidermis. The ligand-mediated cellular uptake outpaces protein degradation resulting in intact antigen delivery. Due to the pivotal role of Langerhans cells in induction of immune responses, this approach of antigen-targeting of tissue-resident immune cells offers a novel way to deliver highly effective vaccines with minimally invasive administration. [ABSTRACT FROM AUTHOR]

Glycosylation represents one of the most abundant posttranslational modification of proteins. Glycosylation products are diverse and are regulated by the cooperative action of various glycosyltransferases, glycosidases, substrates thereof: nucleoside sugars and their transporters, and chaperons. In this article, we focus on a glycosyltransferase, α1,6-fucosyltransferase (Fut8) and its product, the core fucose structure on N-glycans, and summarize the potential protective functions of this structure against emphysema and chronic obstructive pulmonary disease (COPD). Studies of FUT8 and its enzymatic product, core fucose, are becoming an emerging area of interest in various fields of research including inflammation, cancer and therapeutics. This article discusses what we can learn from studies of Fut8 and core fucose by using knockout mice or in vitro studies that were conducted by our group as well as other groups. We also include a discussion of the potential protective functions of the keratan sulfate (KS) disaccharide, namely L4, against emphysema and COPD as a glycomimetic. Glycomimetics using glycan analogs is one of the more promising therapeutics that compensate for the usual therapeutic strategy that involves targeting the genome and the proteome. These typical glycans using KS derivatives as glycomimetics, will likely become a clue to the development of novel and effective therapeutic strategies. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) is the most disease-causative flavivirus worldwide. DENV as a mosquito-borne virus infects human hosts through the skin; however, the initial target cells in the skin remain unclear. In this study, we have investigated whether epidermal Langerhans cells (LCs) play a role in DENV acquisition and dissemination. We have used a human epidermal ex vivo infection model as well as isolated LCs to investigate infection by DENV. Notably, both immature and mature LCs were permissive to DENV infection in vitro and ex vivo, and infection was dependent on C-type lectin receptor langerin because blocking antibodies against langerin significantly reduced DENV infection in vitro and ex vivo. DENV-infected LCs efficiently transmitted DENV to target cells such as dendritic cells. Moreover, DENV exposure increased the migration of LCs from epidermal explants. These results strongly suggest that DENV targets epidermal LCs for infection and dissemination in the human host. These findings could provide potential drug targets to combat the early stage of DENV infection., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

In this study we developed a liposome-based vaccine containing palmitoylated synthetic long peptides (SLP) and alpha galactosylceramide (αGC) to specifically target dendritic cells (DC) for activation of both innate (invariant natural killer T-cells [iNKT]) and adaptive (CD8+ T-cells) players of the immune system. Combination of model tumor specific antigens (gp100/MART-1) formulated as a SLP and αGC in one liposome results in strong activation of CD8+ and iNKT, as measured by IFNγ secretion. Moreover, addition of lipo-Lewis Y (LeY) to the liposomes for C-type lectin targeting increased not only uptake by monocyte-derived dendritic cells (moDC), dermal dendritic cells and Langerhans cells but also enhanced gp100-specific CD8+ T- and iNKT cell activation by human skin-emigrated antigen presenting cells in an ex vivo explant model. Loading of moDC with liposomes containing LeY also showed priming of MART-126−35L specific CD8+ T-cells. In conclusion, chemically linking a lipid tail to a glycan-based targeting moiety and SLP combined with αGC in one liposome allows for easy generation of vaccine formulations that target multiple skin DC subsets and induce tumor antigen specific CD8+ T- and iNKT cells. These liposomes present a new vaccination strategy against tumors.

Sexually transmitted Hepatitis C virus (HCV) infections and high reinfections are a major concern amongst men who have sex with men (MSM) living with HIV-1 and HIV-negative MSM. Immune activation and/or HIV-1 coinfection enhance HCV susceptibility via sexual contact, suggesting that changes in immune cells or external factors are involved in increased susceptibility. Activation of anal mucosal Langerhans cells (LCs) has been implicated in increased HCV susceptibility as activated but not immature LCs efficiently retain and transmit HCV to other cells. However, the underlying molecular mechanism of transmission remains unclear. Here we identified the Heparan Sulfate Proteoglycan Syndecan 4 as the molecular switch, controlling HCV transmission by LCs. Syndecan 4 was highly upregulated upon activation of LCs and interference with Heparan Sulfate Proteoglycans or silencing of Syndecan 4 abrogated HCV transmission. These data strongly suggest that Syndecan 4 mediates HCV transmission by activated LCs. Notably, our data also identified the C-type lectin receptor langerin as a restriction factor for HCV infection and transmission. Langerin expression abrogated HCV infection in HCV permissive cells, whereas langerin expression on the Syndecan 4 expressing cell line strongly decreased HCV transmission to a target hepatoma cell line. These data suggest that the balanced interplay between langerin restriction and Syndecan 4 transmission determines HCV dissemination. Silencing of langerin enhanced HCV transmission whereas silencing Syndecan 4 on activated LCs decreased transmission. Blocking Heparan Sulfate Proteoglycans abrogated HCV transmission by LCs ex vivo identifying Heparan Sulfate Proteoglycans and Syndecan 4 as potential targets to prevent sexual transmission of HCV. Thus, our data strongly suggest that the interplay between receptors promotes or restricts transmission and further indicate that Syndecan 4 is the molecular switch controlling HCV susceptibility after sexual contact.

Since a long time caffeine has been used in pharmaceutical and cosmetic preparations due to its favorable effects on the skin. The aim of this study was to evaluate the topical anti-inflammatory activity (carrageenan-induced paw oedema) of an ointment prepared using a methanolic extract from green beans of C. robusta via histology. Results showed that the treatment with the ointment reduced the paw oedema within 3 and 5 h post-carrageenan administration. The immunohistochemical evaluations of αSMA, Langerin and S100 gave further support to the morphological analysis. Finally, the methanolic extract from green beans of C. robusta proved to possess elevated free radical scavenger capability by DPPH assay, which may contribute to the observed anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

Sexually transmitted Hepatitis C virus (HCV) infections and high reinfections are a major concern amongst men who have sex with men (MSM) living with HIV-1 and HIV-negative MSM. Immune activation and/or HIV-1 coinfection enhance HCV susceptibility via sexual contact, suggesting that changes in immune cells or external factors are involved in increased susceptibility. Activation of anal mucosal Langerhans cells (LCs) has been implicated in increased HCV susceptibility as activated but not immature LCs efficiently retain and transmit HCV to other cells. However, the underlying molecular mechanism of transmission remains unclear. Here we identified the Heparan Sulfate Proteoglycan Syndecan 4 as the molecular switch, controlling HCV transmission by LCs. Syndecan 4 was highly upregulated upon activation of LCs and interference with Heparan Sulfate Proteoglycans or silencing of Syndecan 4 abrogated HCV transmission. These data strongly suggest that Syndecan 4 mediates HCV transmission by activated LCs. Notably, our data also identified the C-type lectin receptor langerin as a restriction factor for HCV infection and transmission. Langerin expression abrogated HCV infection in HCV permissive cells, whereas langerin expression on the Syndecan 4 expressing cell line strongly decreased HCV transmission to a target hepatoma cell line. These data suggest that the balanced interplay between langerin restriction and Syndecan 4 transmission determines HCV dissemination. Silencing of langerin enhanced HCV transmission whereas silencing Syndecan 4 on activated LCs decreased transmission. Blocking Heparan Sulfate Proteoglycans abrogated HCV transmission by LCs ex vivo identifying Heparan Sulfate Proteoglycans and Syndecan 4 as potential targets to prevent sexual transmission of HCV. Thus, our data strongly suggest that the interplay between receptors promotes or restricts transmission and further indicate that Syndecan 4 is the molecular switch controlling HCV susceptibility after sexual contact. [ABSTRACT FROM AUTHOR]

Dendritic cell (DC)–targeting vaccines show great promise in increasing antitumor immunity. Glycan-engineered vaccines facilitate both DC targeting and increased uptake by DCs for processing and presentation to CD4+ and CD8+ T cells to induce tumor-specific T-cell responses. However, the complexity of various DC subsets in skin tissues, expressing different glycan-binding receptors that can mediate vaccine uptake or drainage of vaccines via lymphatics directly to the lymph node–resident DCs, complicates the success of vaccines. Moreover, the influx of inflammatory immune cells to the site of vaccination, such as monocytes that differentiate to DCs and coexpress glycan-binding receptors, may contribute to the strength of DC-targeting glycovaccines for future clinical use. [ABSTRACT FROM AUTHOR]

Indeterminate cell tumor (ICT) is a rare neoplastic dendritic cell disorder that has been poorly defined due to its rarity and poorly understood histogenesis and pathogenesis. It is characterized by a proliferation of dendritic cells, which mimic Langerhans cells immunophenotypically (positive for CD1a and S-100 protein), but lack Birbeck granules characteristic of Langerhans cells. The clinical, morphologic, immunophenotypic, and ultrastructural features of 5 ICT cases are reported in an attempt to further define ICT and to examine the postulated relationship between indeterminate cells and Langerhans cells. Four of 5 patients were females, and 4 of 5 were older than 68 years. Three of 5 patients had cutaneous lesions, whereas 2 presented with cervical lymph node involvement. Two patients had a possible association with lymphoma: first patient had a history of progressive follicular lymphoma that led to patient's demise and the second patient had unexplained systemic lymphadenopathy and died 1 week after the biopsy. All 5 ICT cases expressed CD1a and S-100 protein, but lacked Langerin expression and Birbeck granules ultrastructurally. Interestingly, a t(14;18) was detected by fluorescence in situ hybridization in the ICT cells of the patient with previous follicular lymphoma and a monoclonal kappa light chain gene rearrangement was detected by polymerase chain reaction in the patient with systemic lymphadenopathy. In both cases, there was no morphologic or immunophenotypic evidence of a concurrent B-cell lymphoma. In conclusion, ICT is a rare neoplasm that can occur de novo or in association with a B-cell lymphoma, possibly as a result of B-cell dedifferentiation caused by relatively unknown mechanisms. Finally, Langerin immunostaining may be used as a surrogate marker for the ultrastructural demonstration of Birbeck granules, the absence of which represents a strong diagnostic criterion for ICT.

Indeterminate cell tumor (ICT) is a rare neoplastic dendritic cell disorder that has been poorly defined due to its rarity and poorly understood histogenesis and pathogenesis. It is characterized by a proliferation of dendritic cells, which mimic Langerhans cells immunophenotypically (positive for CD1a and S-100 protein), but lack Birbeck granules characteristic of Langerhans cells. The clinical, morphologic, immunophenotypic, and ultrastructural features of 5 ICT cases are reported in an attempt to further define ICT and to examine the postulated relationship between indeterminate cells and Langerhans cells. Four of 5 patients were females, and 4 of 5 were older than 68 years. Three of 5 patients had cutaneous lesions, whereas 2 presented with cervical lymph node involvement. Two patients had a possible association with lymphoma: first patient had a history of progressive follicular lymphoma that led to patient's demise and the second patient had unexplained systemic lymphadenopathy and died 1 week after the biopsy. All 5 ICT cases expressed CD1a and S-100 protein, but lacked Langerin expression and Birbeck granules ultrastructurally. Interestingly, a t(14;18) was detected by fluorescence in situ hybridization in the ICT cells of the patient with previous follicular lymphoma and a monoclonal kappa light chain gene rearrangement was detected by polymerase chain reaction in the patient with systemic lymphadenopathy. In both cases, there was no morphologic or immunophenotypic evidence of a concurrent B-cell lymphoma. In conclusion, ICT is a rare neoplasm that can occur de novo or in association with a B-cell lymphoma, possibly as a result of B-cell dedifferentiation caused by relatively unknown mechanisms. Finally, Langerin immunostaining may be used as a surrogate marker for the ultrastructural demonstration of Birbeck granules, the absence of which represents a strong diagnostic criterion for ICT.

Background: The clinical presentation of Langerhans cell histiocytosis (LCH) is heterogeneous ranging from single-organ involvement to systemic disease causing substantial morbidity and mortality. We describe an unusual course of severe multisystem LCH with spontaneous remission. Case Presentation: We report on a 45-year-old Caucasian woman with cervical cancer, FIGO stage IVB. Five months after the end of combined radiochemotherapy and brachytherapy, the patient was readmitted because of severe dysuria. Sterile leukocyturia was seen, and cystoscopy revealed only 3 unspecific small mucosal lesions compatible with postradiation cystitis. Incidentally, a computed tomography (CT) scan of the body showed diffuse micronodular and cystic lesions in lungs and hypodense lesions in the liver. Biopsies revealed infiltrations of CD1a and Langerin (CD207)-positive histiocytes in the lung, liver, and bladder. Additionally, positron emission tomography-CT (PET-CT) was compatible with bone involvement. Retrospective analysis revealed that the increase in alkaline phosphatase might have been a surrogate of bone marrow infiltration with osseous activity. Repeated pneumothoraces occurred, and only one course of vinblastine-prednisolone could be applied. Despite ongoing tobacco consumption and without further therapy, PET-CT showed considerable remission 2 months later. However, despite stable remission, documented by serial PET and conventional CT scans, persistent infiltration of the bladder by Langerhans histiocytes could still be demonstrated 17 months later. Unfortunately, cervical cancer recurred and progressed. Conclusion: Multisystem LCH may rapidly occur, may be oligosymptomatic and, even in high-risk cases, remission without specific therapy might occur. Whether alkaline phosphatase might be a surrogate to monitor osseous disease activity has to be further explored.

ABSTRACT Staphylococcus aureus is a major cause of skin and soft tissue infections and aggravator of the inflammatory skin disease atopic dermatitis (AD [eczema]). Epicutaneous exposure to S. aureus induces Th17 responses through skin Langerhans cells (LCs), which paradoxically contribute to host defense but also to AD pathogenesis. The molecular mechanisms underlying the interaction between S. aureus and LCs are poorly understood. Here we demonstrate that human LCs directly interact with S. aureus through the pattern recognition receptor langerin (CD207). Human, but not mouse, langerin interacts with S. aureus through the conserved β-N-acetylglucosamine (GlcNAc) modifications on wall teichoic acid (WTA), thereby discriminating S. aureus from other staphylococcal species. Importantly, the specific S. aureus WTA glycoprofile strongly influences the level of proinflammatory cytokines that are produced by in vitro-generated LCs. Finally, in a murine epicutaneous infection model, S. aureus strongly upregulated transcripts of Cxcl1, Il6, and Il17, which required the presence of both human langerin and WTA β-GlcNAc. Our findings provide molecular insight into the unique proinflammatory capacities of S. aureus in relation to skin inflammation. IMPORTANCE The bacterium Staphylococcus aureus is an important cause of skin infections and is also associated with the occurrence and severity of eczema. Langerhans cells (LCs), a specific subset of skin immune cells, participate in the immune response to S. aureus, but it is yet unclear how LCs recognize S. aureus. Therefore, we investigated the molecular mechanism underlying the interaction between LCs and S. aureus. We identified that wall teichoic acid, an abundant polymer on the S. aureus surface, is recognized by langerin, a receptor unique to LCs. This interaction allows LCs to discriminate S. aureus from other related staphylococcal species and initiates a proinflammatory response similar to that observed in patients with eczema. Our data therefore provide important new insights into the relationship between S. aureus, LCs, and eczema.

Introduction: Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial lung disease characterized by the accumulation of Langerhans cells within the lung tissue. The diagnosis of PLCH traditionally involves clinical, radiological, and lung biopsy histopathological evaluations., Case Presentation: We present 2 cases where the diagnosis of PLCH was confirmed through the analysis of bronchoalveolar lavage (BAL) fluid cytology using immunoperoxidase technique, highlighting the significance of this minimally invasive technique in the diagnostic process. Clinical and radiological examination suggested advanced interstitial lung disease characterized by a fibrocystic pattern in both cases. The cytologic analysis of the BAL fluid revealed typical histiocytes with longitudinal grooves and eosinophils, which was better seen on liquid-based cytology (LBC) smears. ICC with CD1a, Langerin, and S-100 confirmed the diagnosis of PLCH., Conclusion: Detecting PLCH through the examination of BAL cytology poses challenges, yet it is achievable, particularly with the assistance of LBC and ICC., (© 2024 S. Karger AG, Basel.)

Background: Epicutaneous sensitization is an important route of immunization for allergens in atopic diseases; however, studies have also shown that application with protein on the intact skin induces antigen‐specific tolerance. Langerhans cells (LCs) play an immunosuppressive role in several inflammatory skin diseases and mouse models, and the role of LCs in the skin‐induced tolerance is not fully understood. Methods: Langerin‐DTA mice that were deficient in LCs were utilized to produce the model of skin‐induced tolerance to ovalbumin (OVA). Binding of Langerin to OVA was analyzed by enzyme‐linked immunosorbent assay, flow cytometry, and immunofluorescence. Homozygous Langerin‐DTR mice that were deficient in Langerin were introduced to assess the role of Langerin in the skin‐induced tolerance. Results: Application with OVA onto the intact, but not tape‐stripped, skin attenuated the production of OVA‐specific IgE, IgG1, and IgG2a induced by subsequent subcutaneous immunization with OVA, and the inhibitory effects were abolished in Langerin‐DTA mice. In contrast to the tape‐stripped skin, the intact skin induced the production of IL‐10 by LCs in draining lymph node after application with OVA. Langerin could bind OVA, and homozygous Langerin‐DTR mice demonstrated similar humoral and cellular immune responses in the model of skin‐induced tolerance compared to wide‐type mice. Conclusion: Our data suggested that LCs were critical in the intact skin‐induced tolerance to protein antigen via Langerin, and LCs might be targeted via Langerin to regulate the immune responses in systemic and (or) skin inflammatory diseases. [ABSTRACT FROM AUTHOR]

Objective: Langerhans cell histiocytosis (LCH) is a rare disease affecting predominantly children and young adults but can be found in any age group. Diagnosis of LCH is often difficult and can be delayed because of its rarity. The present study highlights the cytomorphological features in a large cohort of cases. An accurate cytological diagnosis may avoid unnecessary biopsy and guide appropriate management. Method: Fourty seven (47) cases of LCH diagnosed on cytological material & fine‐needle aspiration (FNA) over a period of 14 years (2003‐2016) were retrieved from the archives. The cytological smears were evaluated and microscopic findings collected by semi‐quantitative assessment done by two different pathologists Result: The age at the diagnosis of the patients ranged from 9 months to 28 years. The majority of cases were in the age group of 0‐5 years. The most common site was head and neck region, which included cervical lymphadenopathy and scalp swelling. Two cases were diagnosed each from inguinal lymph node and bronchio‐alveolar lavage (BAL). Cytological smears in the majority of the cases were moderate to highly cellular (58%) and showing abundant Langerhans cell in (72%) of cases. Areas of necrosis were seen in 38%, while 78% of cases showed giant cells. The majority of cases showed mild eosinophilia (61%), sparse lymphocytosis (83%) and mild neutrophilic infiltration (64%). There were 1‐2 mitoses per 10 high power field in 12 cases (25.5%). No abnormal mitoses were identified. Conclusion: The presence of cells with features of Langerhans cells associated with the expression of selected immunohistochemical markers allow the diagnosis of LCH on cytological samples, sparing more invasive procedure as a biopsy. Langerhans cell histiocytosis is a rare disorder. This study describes in details the cytological features of this entity useful to the pathologist when the clinical picture is suspicious of this disease. [ABSTRACT FROM AUTHOR]

Nasopharyngeal cancer (NPC) is associated with Epstein-Barr virus (EBV) and EBV antigen may be utilized for therapeutic purposes, including targeting of dendritic cells (DCs). Although DCs may be present in NPC, the information is limited and not up-to-date with current knowledge on DC subsets. In the present study, biopsies from untreated NPC were obtained and subjected to multicolor flow-cytometry focusing on DC subtype markers: CD123 for plasmacytoid DCs (pDCs); and CD1c and CD141 for myeloid DCs (mDCs). Furthermore, subset-specific expression of the C-lectin receptor (CLR) CD207 (also termed langerin) was assessed. pDCs and mDCs were detected in the NPC lesions, contributing to a frequency mean average of 0.78% of CD45+ leukocytes in situ. Different subpopulations, previously not described in NPC, were observed, including: CD123+ pDCs; CD1c+ mDCs; CD141+ mDCs; and CD1c−CD141− mDCs. A high frequency of CD1c+ mDCs expressing CD207 was observed, compared with other subsets. In conclusion, different DC subsets are present in NPC lesions. The CLR CD207, a selective endocytic marker on CD1c+ mDCs, may be targeted for therapeutic purposes to facilitate cross-presentation of antigens and aid cell-mediated antitumor effects. [ABSTRACT FROM AUTHOR]

Peri-implantitis is a destructive inflammatory process affecting tissues surrounding dental implants and it is considered a new global health concern. Human studies have suggested that the frequencies of Langerhans cells (LCs), the main antigen-presenting cells (APCs) of the oral epithelium, are dysregulated around the implants. Since LCs play a role in regulating oral mucosal homeostasis, we studied the impact of dental titanium implants on LC differentiation using a novel murine model. We demonstrate that whereas the percentage of LC precursors (CD11c+MHCII+) increased in the peri-implant epithelium, the frequencies of LCs (CD11c+MHCII+EpCAM+langerin+) were significantly reduced. Instead, a population of partially developed LCs expressing CD11c+MHCII+EpCAM+ but not langerin evolved in the peri-implant mucosa, which was also accompanied by a considerable leukocyte infiltrate. In line with the increased levels of LC precursors, expression of CCL2 and CCL20, chemokines mediating their translocation to the epithelium, was elevated in the peri-implant epithelium. However, expression of TGF-β1, the major cytokine driving final differentiation of LCs, was reduced in the epithelium. Further analysis revealed that while the expression of the TGF-β1 canonical receptor activing-like kinase (ALK)5 was upregulated, expression of its non-canonical receptor ALK3 was decreased. Since titanium ions releasing from implants were proposed to alter APC function, we next analyzed the impact of such ions on TGF-β1-induced LC differentiation cultures. Concurring with the in vivo studies, the presence of titanium ions resulted in the generation of partially developed LCs that express CD11c+MHCII+EpCAM+ but failed to upregulate langerin expression. Collectively, these findings suggest that titanium dental implants have the capacity to impair the development of oral LCs and might subsequently dysregulate immunity in the peri-implant mucosa.

Bloodstream infections induce considerable morbidity, high mortality, and represent a significant burden of cost in health care; however, our understanding of the immune response to bacteremia is incomplete. Langerin+ CD8α+ dendritic cells (DCs), residing in the marginal zone of the murine spleen, have the capacity to cross-prime CD8+ T cells and produce IL-12, both of which are important components of antimicrobial immunity. Accordingly, we hypothesized that this DC subset may be a key promoter of adaptive immune responses to blood-borne bacterial infections. Utilizing mice that express the diphtheria toxin receptor under control of the langerin promoter, we investigated the impact of depleting langerin+ CD8α+ DCs in a murine model of intravenous infection with Mycobacterium bovis bacille Calmette–Guerin (BCG). In the absence of langerin+ CD8α+ DCs, the immune response to blood-borne BCG infection was diminished: bacterial numbers in the spleen increased, serum IL-12p40 decreased, and delayed CD8+ T cell activation, proliferation, and IFN-γ production was evident. Our data revealed that langerin+ CD8α+ DCs play a pivotal role in initiating CD8+ T cell responses and IL-12 production in response to bacteremia and may influence the early control of systemic bacterial infections.

β-(1→3)-Glucans can be found as structural polysaccharides in cereals, in algae or as exo-polysaccharides secreted on the surfaces of mushrooms or fungi. Research has now established that β-(1→3)-glucans can trigger different immune responses and act as efficient immunostimulating agents. They constitute prevalent sources of carbons for microorganisms after subsequent recognition by digesting enzymes. Nevertheless, mechanisms associated with both roles are not yet clearly understood. This review focuses on the variety of elucidated molecular interactions that involve these natural or synthetic polysaccharides and their receptors, i.e., Dectin-1, CR3, glycolipids, langerin and carbohydrate-binding modules.

Highlights • A glycosaminoglycan, keratan sulfate, may be involved in COPD development. • Keratan sulfate disaccharide L4 has anti-inflammatory activity and suppresses COPD. • Langerin is a potential L4 receptor. • L4 oligomers show over 1000-fold higher affinity toward langerin than the L4 monomer. Abstract Glycosylation is profoundly involved in various diseases, and interactions between glycan binding proteins and their sugar ligands are plausible drug targets. Keratan sulfate (KS), a glycosaminoglycan, is downregulated in lungs by cigarette smoking, suggesting that KS is involved in smoking-related diseases, such as chronic obstructive pulmonary disease (COPD). We found that a highly sulfated KS disaccharide, L4, suppresses lung inflammation and is effective against COPD and its exacerbation in mouse models. Its anti-inflammatory activity was comparable to that of a steroid. As a possible mechanism, langerin, a C-type lectin receptor (CLR) expressed in dendritic cells, was suggested to function as an L4 receptor. Oligomeric L4 derivatives were chemically designed to create new ligands with higher affinity and activity. The synthetic L4 oligomers bound to langerin with over 1000-fold higher affinity than the L4 monomer, suggesting that these compounds are effective drug candidates against COPD and inflammatory diseases. [ABSTRACT FROM AUTHOR]

Peri-implantitis is a destructive inflammatory process affecting tissues surrounding dental implants and it is considered a new global health concern. Human studies have suggested that the frequencies of Langerhans cells (LCs), the main antigen-presenting cells (APCs) of the oral epithelium, are dysregulated around the implants. Since LCs play a role in regulating oral mucosal homeostasis, we studied the impact of dental titanium implants on LC differentiation using a novel murine model. We demonstrate that whereas the percentage of LC precursors (CD11c+MHCII+) increased in the peri-implant epithelium, the frequencies of LCs (CD11c+MHCII+EpCAM+langerin+) were significantly reduced. Instead, a population of partially developed LCs expressing CD11c+MHCII+EpCAM+ but not langerin evolved in the peri-implant mucosa, which was also accompanied by a considerable leukocyte infiltrate. In line with the increased levels of LC precursors, expression of CCL2 and CCL20, chemokines mediating their translocation to the epithelium, was elevated in the peri-implant epithelium. However, expression of TGF-β1, the major cytokine driving final differentiation of LCs, was reduced in the epithelium. Further analysis revealed that while the expression of the TGF-β1 canonical receptor activing-like kinase (ALK)5 was upregulated, expression of its non-canonical receptor ALK3 was decreased. Since titanium ions releasing from implants were proposed to alter APC function, we next analyzed the impact of such ions on TGF-β1-induced LC differentiation cultures. Concurring with the in vivo studies, the presence of titanium ions resulted in the generation of partially developed LCs that express CD11c+MHCII+EpCAM+ but failed to upregulate langerin expression. Collectively, these findings suggest that titanium dental implants have the capacity to impair the development of oral LCs and might subsequently dysregulate immunity in the peri-implant mucosa. [ABSTRACT FROM AUTHOR]

Background Langerin, a C-type lectin receptor (CLR) expressed in a subset of dendritic cells (DCs), binds to glycan ligands for pathogen capture and clearance. Previous studies revealed that langerin has an unusual binding affinity toward 6-sulfated galactose (Gal), a structure primarily found in keratan sulfate (KS). However, details and biological outcomes of this interaction have not been characterized. Based on a recent discovery that the disaccharide L4, a KS component that contains 6-sulfo-Gal, exhibits anti-inflammatory activity in mouse lung, we hypothesized that L4-related compounds are useful tools for characterizing the langerin-ligand interactions and their therapeutic application. Methods We performed binding analysis between purified long and short forms of langerin and a series of KS disaccharide components. We also chemically synthesized oligomeric derivatives of L4 to develop a new high-affinity ligand of langerin. Results We show that the binding critically requires the 6-sulfation of Gal and that the long form of langerin displays higher affinity than the short form. The synthesized trimeric (also designated as triangle or Tri) and polymeric (pendant) L4 derivatives displayed over 1000-fold higher affinity toward langerin than monomeric L4. The pendant L4, but not the L4 monomer, was found to effectively transduce langerin signaling in a model cell system. Conclusions L4 is a specific ligand for langerin. Oligomerization of L4 unit increased the affinity toward langerin. General significance These results suggest that oligomeric L4 derivatives will be useful for clarifying the langerin functions and for the development of new glycan-based anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

Bloodstream infections induce considerable morbidity, high mortality, and represent a significant burden of cost in health care; however, our understanding of the immune response to bacteremia is incomplete. Langerin+ CD8α+ dendritic cells (DCs), residing in the marginal zone of the murine spleen, have the capacity to cross-prime CD8+ T cells and produce IL-12, both of which are important components of antimicrobial immunity. Accordingly, we hypothesized that this DC subset may be a key promoter of adaptive immune responses to blood-borne bacterial infections. Utilizing mice that express the diphtheria toxin receptor under control of the langerin promoter, we investigated the impact of depleting langerin+ CD8α+ DCs in a murine model of intravenous infection with Mycobacterium bovis bacille Calmette-Guerin (BCG). In the absence of langerin+ CD8α+ DCs, the immune response to blood-borne BCG infection was diminished: bacterial numbers in the spleen increased, serum IL-12p40 decreased, and delayed CD8+ T cell activation, proliferation, and IFN-γ production was evident. Our data revealed that langerin+ CD8α+ DCs play a pivotal role in initiating CD8+ T cell responses and IL-12 production in response to bacteremia and may influence the early control of systemic bacterial infections. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis (LCH) is a rare multi-system disease. It presents infrequently as a childhood orbital tumor, and can mimic more common inflammatory orbital disease processes. We report the clinical, histopathological, and electron microscopic findings of orbital LCH in an 18-month-old child, along with a review of the recent literature regarding molecular pathogenetic analysis of LCH. The child presented with a two-week history of progressive left periorbital edema and redness. He was initially diagnosed and treated empirically for bacterial periorbital cellulitis, but subsequently underwent ophthalmological consultation after he failed to improve. Histopathological examination of an orbital biopsy specimen revealed numerous Langerhans-type cells, which stain positive for CD1A and CD207 (langerin). Electron microscopic examination demonstrated characteristic Birbeck granules within the Langerhans-type cells. Three year follow-up did not demonstrate recurrence or disease progression. [ABSTRACT FROM AUTHOR]

Background Indeterminate dendritic cell tumor (IDCT) is an extremely rare hematologic disorder with poorly understood pathogenesis. Occasionally encountered by hematologists, unusual presentations of IDCT have not been reported in the spine literature. Methods We report a 51-year-old man who presented with a 3-month history of progressively worsening axial thoracic back pain radiating to his sides. Magnetic resonance imaging revealed a 3-cm enhancing mass at the T9 vertebral body with an exophytic component causing significant canal stenosis. Initial percutaneous biopsy revealed histiocytic sarcoma. Results The patient underwent exploratory thoracotomy and en bloc resection of the lesion with T8-10 fusion. Final pathology results revealed IDCT with fibrosis. IDCT immunostaining was partially positive for Langerhans cell marker (positive for S100 and CD1a, but lacked Birbeck granules and Langerin stain) and partially positive for blastic plasmacytoid dendritic cell neoplasm. Additionally, it was positive for CD45, CD68, and CD163. Lymphadenopathy was absent in this patient. Conclusions Although first reported in the 1980s, IDCT has been omitted from most classifications owing to its rarity. Hematologists have debated the cell of origin; it is believed to comprise pre–Langerhans cells, as Birbeck granules are acquired after migration to the epidermis. IDCT remains of indeterminate origin. We report the first case of spinal IDCT. Familiarity with the histologic features is warranted to ensure accurate diagnosis and appropriate treatment. [ABSTRACT FROM AUTHOR]

Studies on human genetic variations are a useful source of knowledge about human immunodeficiency virus (HIV)-1 infection. The Langerin protein, found at the surface of Langerhans cells, has an important protective role in HIV-1 infection. Differences in Langerin function due to host genetic factors could influence susceptibility to HIV-1 infection. To verify the frequency of mutations in the Langerin gene, 118 samples from HIV-1-infected women and 99 samples from HIV-1-uninfected individuals were selected for sequencing of the promoter and carbohydrate recognition domain (CRD)-encoding regions of the Langerin gene. Langerin promoter analysis revealed two single nucleotide polymorphisms (SNPs) and one mutation in both studied groups, which created new binding sites for certain transcription factors, such as NFAT5, HOXB9.01 and STAT6.01, according to MatInspector software analysis. Three SNPs were observed in the CRD-encoding region in HIV-1-infected and uninfected individuals: p.K313I, c.941C>T and c.983C>T. This study shows that mutations in the Langerin gene are present in the analysed populations at different genotypic and allelic frequencies. Further studies should be conducted to verify the role of these mutations in HIV-1 susceptibility.