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A novel engineered CCL20 locked dimer (CCL20LD) is nearly identical to the naturally occurring chemokine CCL20 but blocks CCR6-mediated chemotaxis and offers a new approach to treat the diseases of psoriasis and psoriatic arthritis. Methods for quantifying CCL20LD serum levels are needed to assess pharmacokinetics parameters and evaluate drug delivery, metabolism, and toxicity. Existing ELISA kits fail to discriminate between CCL20LD and the natural chemokine, CCL20WT (the wild type monomer). Herein, we tested several available CCL20 monoclonal antibodies to be able to identify one clone that can be used both as a capture and a detection antibody (with biotin-labeling) to specifically detect CCL20LD with high specificity. After validation using recombinant proteins, the CCL20LD-selective ELISA was used to analyze blood samples from CCL20LD treated mice, demonstrating the utility of this novel assay for preclinical development of a biopharmaceutical lead compound for psoriatic disease.

ObjectiveChronic pancreatitis (CP) is a potentially fatal disease of the exocrine pancreas, with no specific or effective approved therapies. Due to difficulty in accessing pancreas tissues, little is known about local immune responses or pathogenesis in human CP. We sought to characterise pancreatic immune responses using tissues derived from patients with different aetiologies of CP and non-CP organ donors in order to identify key signalling molecules associated with human CP.DesignWe performed single-cell level cellular indexing of transcriptomes and epitopes by sequencing and T-cell receptor (TCR) sequencing of pancreatic immune cells isolated from organ donors, hereditary and idiopathic patients with CP who underwent total pancreatectomy. We validated gene expression data by performing flow cytometry and functional assays in a second patient with CP cohort.ResultsDeep single-cell sequencing revealed distinct immune characteristics and significantly enriched CCR6+ CD4+ T cells in hereditary compared with idiopathic CP. In hereditary CP, a reduction in T-cell clonality was observed due to the increased CD4+ T (Th) cells that replaced tissue-resident CD8+ T cells. Shared TCR clonotype analysis among T-cell lineages also unveiled unique interactions between CCR6+ Th and Th1 subsets, and TCR clustering analysis showed unique common antigen binding motifs in hereditary CP. In addition, we observed a significant upregulation of the CCR6 ligand (CCL20) expression among monocytes in hereditary CP as compared with those in idiopathic CP. The functional significance of CCR6 expression in CD4+ T cells was confirmed by flow cytometry and chemotaxis assay.ConclusionSingle-cell sequencing with pancreatic immune cells in human CP highlights pancreas-specific immune crosstalk through the CCR6-CCL20 axis, a signalling pathway that might be leveraged as a potential future target in human hereditary CP.

Bile acids (BAs), produced in the liver and further transformed in the gut, are cholesterol-derived molecules involved in essential physiological processes. Recent studies suggest that BAs regulate T helper 17 cell function, but the underlying mechanism of this action and their therapeutic value in disease models remains unclear. Using an IL-23 minicircle DNA-based murine model of psoriasiform dermatitis, we showed that oral administration of secondary BAs, including lithocholic acid (LCA), deoxycholic acid, and 3-oxoLCA, significantly improved psoriasiform dermatitis without inducing apparent hepatotoxicity. Of the BAs tested, LCA possessed the greatest potency in treating psoriasiform dermatitis. Intravenous administration of LCA at a much lower dosage (compared with oral treatment) showed a comparable antipsoriatic effect and markedly suppressed the IL-17A response. Ex vivo experiments revealed that LCA reduced IL-17A production in IL-23-stimulated murine T cells in the absence of BA receptors TGR5 or FXR. Strikingly, BAs inhibited CCL20 expression in keratinocytes, which led to reduced migration of CCR6-expressing Jurkat cells cultured in the conditioned medium of stimulated keratinocytes. Thus, BAs improve psoriasiform dermatitis with minimal toxicity via direct inhibition of IL-17A production and blockade of CCL20-mediated trafficking, supporting the potential use of BAs in psoriasis.

Objective: The purpose of this study was to compare eight weeks of exposure to sunlight and Home-Based Pilates Training serum vitamin D, CCL20, and the body composition of women with multiple sclerosis. Materials and Methods: This study was a quasi-experimental study. Among women with Multiple sclerosis (with2-5EDSS), 44 were purposefully and voluntarily selected and randomly divided into three groups: Pilates at home) n=15), Pilates exposed to the sun (n=15) and control (n=14) were divided. The training program consisted of three sessions per week for eight weeks, consisting of two parts, Pilates training at home and Pilates training in the environment. An exercise program on the DVD was provided. The Serum vitamin D, CCL20 indices, and body composition of patients with MS were measured 48 hours before and after eight Pilates exercises at home and under sunlight. To analyze the data, analysis of covariance and Bonferroni post hoc test, SPSS software, and P= 0.05 significance level. Results: Comparing the results in the two stages showed that there was a significant difference between CCL20 (P= 0.001), serum vitamin D (P= 0.001), BMI (P= 0.001), weight (P= 0.001) and WHR (P= 0.001) indices of women with MS in the studied groups. These differences were only between the training groups and the control group. However, there was a significant difference in the CCL20 index and serum vitamin D between the two training groups (Respectively P= 0.037, P= 0.001). Conclusion: Patients with MS can improve their vitamin D level and weight-related and inflammatory indicators by using Pilates exercises exposed to sunlight and at home with minimal cost. [ABSTRACT FROM AUTHOR]

BACKGROUND: Glucocorticoids (GCs) are generally envisioned as immunosuppressive, but in conditions such as rosacea and perioral dermatitis they can lead to increased skin inflammation. In lung epithelia, GCs promote expression of the proinflammatory cytokine CCL20, which contributes to steroid-resistant asthma. In the skin, CCL20 stimulates inflammation by recruiting T helper 17 T lymphocytes and dendritic cells, and is elevated in papulopustular rosacea. OBJECTIVES: To understand if, and how, GCs affect CCL20 expression in human keratinocytes. CCL20 expression was assessed by quantitative reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. METHODS: Selective inhibition of candidate genes and signalling pathways was performed using RNA interference and chemical inhibitors. The binding of activated GC receptor to genomic DNA was determined by chromatin immunoprecipitation, and enhancer activity of genomic sequences was measured with a reporter assay. RESULTS: We found that GC treatment increased CCL20 expression in human keratinocytes and murine skin, both in the undisturbed state and with tumour necrosis factor-α stimulation. GC repressed proinflammatory signalling pathways, including nuclear factor kappa B and p38/mitogen-activated protein kinase, but these inhibitory effects were opposed by the direct binding of activated GC receptor to the CCL20 enhancer, promoting CCL20 expression. CONCLUSIONS: Viewed together, these findings demonstrate a mechanism by which GCs induce expression of CCL20 in keratinocytes, which may contribute to the inflammation seen in steroid-exacerbated skin conditions.

BackgroundThe activation of the EGFR/Ras-signalling pathway in tumour cells induces a distinct chemokine repertoire, which in turn modulates the tumour microenvironment.MethodsThe effects of EGFR/Ras on the expression and translation of CCL20 were analysed in a large set of epithelial cancer cell lines and tumour tissues by RT-qPCR and ELISA in vitro. CCL20 production was verified by immunohistochemistry in different tumour tissues and correlated with clinical data. The effects of CCL20 on endothelial cell migration and tumour-associated vascularisation were comprehensively analysed with chemotaxis assays in vitro and in CCR6-deficient mice in vivo.ResultsTumours facilitate progression by the EGFR/Ras-induced production of CCL20. Expression of the chemokine CCL20 in tumours correlates with advanced tumour stage, increased lymph node metastasis and decreased survival in patients. Microvascular endothelial cells abundantly express the specific CCL20 receptor CCR6. CCR6 signalling in endothelial cells induces angiogenesis. CCR6-deficient mice show significantly decreased tumour growth and tumour-associated vascularisation. The observed phenotype is dependent on CCR6 deficiency in stromal cells but not within the immune system.ConclusionWe propose that the chemokine axis CCL20-CCR6 represents a novel and promising target to interfere with the tumour microenvironment, and opens an innovative multimodal strategy for cancer therapy.

BackgroundAutosomal dominant anhidrotic ectodermal dysplasia with immune deficiency (AD EDA-ID) is caused by heterozygous point mutations at or close to serine 32 and serine 36 or N-terminal truncations in IκBα that impair its phosphorylation and degradation and thus activation of the canonical nuclear factor κ light chain enhancer of activated B cells (NF-κB) pathway. The outcome of hematopoietic stem cell transplantation is poor in patients with AD EDA-ID despite achievement of chimerism. Mice heterozygous for the serine 32I mutation in IκBα have impaired noncanonical NF-κB activity and defective lymphorganogenesis.ObjectiveWe sought to establish genotype-phenotype correlation in patients with AD EDA-ID.MethodsA disease severity scoring system was devised. Stability of IκBα mutants was examined in transfected cells. Immunologic, biochemical, and gene expression analyses were performed to evaluate canonical and noncanonical NF-κB signaling in skin-derived fibroblasts.ResultsDisease severity was greater in patients with IκBα point mutations than in those with truncation mutations. IκBα point mutants were expressed at significantly higher levels in transfectants compared with truncation mutants. Canonical NF-κB-dependent IL-6 secretion and upregulation of the NF-κB subunit 2/p100 and RELB proto-oncogene, NF-κB subunit (RelB) components of the noncanonical NF-κB pathway were diminished significantly more in patients with point mutations compared with those with truncations. Noncanonical NF-κB-driven generation of the transcriptionally active p100 cleavage product p52 and upregulation of CCL20, intercellular adhesion molecule 1 (ICAM1), and vascular cell adhesion molecule 1 (VCAM1), which are important for lymphorganogenesis, were diminished significantly more in LPS plus α-lymphotoxin β receptor-stimulated fibroblasts from patients with point mutations compared with those with truncations.ConclusionsIκBα point mutants accumulate at higher levels compared with truncation mutants and are associated with more severe disease and greater impairment of canonical and noncanonical NF-κB activity in patients with AD EDA-ID.

Objective: The study aimed to investigate the potentiality of chemokines, including MCP-1, CCL15, CCL20, and CXCL14, as biomarkers for differential diagnosis between benign tumors and ovarian cancer (OC). Methods: A cross-sectional study was conducted in women aged >18 years who had adnexal masses treated with elective surgery at the HRH Maha Chakri Sirindhorn Medical Center, Srinakharinwirot University, between 2020 and 2021. The preoperative MCP-1, CCL15, CCL20, and CXCL14 serum levels were measured using a sandwich enzyme-linked immunosorbent assay. Preoperative diagnosis was defined according to the risk of malignancy index. The histological diagnosis and cancer subtype were confirmed using pathological specimens. Results: Ninety-eight participants were preoperatively diagnosed with malignant tumors. The pathological diagnosis confirmed OC in 33 patients and disclosed 27 misdiagnosed cases, of which endometriotic cyst was the most common (44.44%). CCL20 and CA125 serum levels were significantly higher in the patients with cancer than in those with benign. In addition, CCL20 level could differentiate between benign and early-stage malignancy. Furthermore, only CCL20 levels could distinguish endometriotic cysts from OC, whereas CA125 levels could not. Concordant with the serum protein level, the increased mRNA level of CCL20 was observed in ovarian cancers comparing with that in benign tissues. We found that CCL20 levels could differentiate between benign tumors and OC with 60.61% sensitivity and 75.44% specificity at the optimal cutoff value of 38.79 pg/ml. Finally, the logistic regression model integrating CCL20, CA125, and menopause status promoted diagnostic accuracy by increasing the specificity to 91.23%. Conclusions: Our study revealed the potential usefulness of CCL20 level as a biomarker for diagnosing early-stage OC with endometriosis differentiation. We recommend further studies to confirm the accuracy of CCL20 levels with the current diagnosis in a large patient sample. [ABSTRACT FROM AUTHOR]

ObjectiveThe study aimed to investigate the potentiality of chemokines, including MCP-1, CCL15, CCL20, and CXCL14, as biomarkers for differential diagnosis between benign tumors and ovarian cancer (OC).MethodsA cross-sectional study was conducted in women aged >18 years who had adnexal masses treated with elective surgery at the HRH Maha Chakri Sirindhorn Medical Center, Srinakharinwirot University, between 2020 and 2021. The preoperative MCP-1, CCL15, CCL20, and CXCL14 serum levels were measured using a sandwich enzyme-linked immunosorbent assay. Preoperative diagnosis was defined according to the risk of malignancy index. The histological diagnosis and cancer subtype were confirmed using pathological specimens.ResultsNinety-eight participants were preoperatively diagnosed with malignant tumors. The pathological diagnosis confirmed OC in 33 patients and disclosed 27 misdiagnosed cases, of which endometriotic cyst was the most common (44.44%). CCL20 and CA125 serum levels were significantly higher in the patients with cancer than in those with benign. In addition, CCL20 level could differentiate between benign and early-stage malignancy. Furthermore, only CCL20 levels could distinguish endometriotic cysts from OC, whereas CA125 levels could not. Concordant with the serum protein level, the increased mRNA level of CCL20 was observed in ovarian cancers comparing with that in benign tissues. We found that CCL20 levels could differentiate between benign tumors and OC with 60.61% sensitivity and 75.44% specificity at the optimal cutoff value of 38.79 pg/ml. Finally, the logistic regression model integrating CCL20, CA125, and menopause status promoted diagnostic accuracy by increasing the specificity to 91.23%.ConclusionsOur study revealed the potential usefulness of CCL20 level as a biomarker for diagnosing early-stage OC with endometriosis differentiation. We recommend further studies to confirm the accuracy of CCL20 levels with the current diagnosis in a large patient sample.

Regulatory T cells (Tregs) are required to establish immune tolerance to commensal microbes. Tregs accumulate abruptly in the skin during a defined window of postnatal tissue development. However, the mechanisms mediating Treg migration to neonatal skin are unknown. Here we show that hair follicle (HF) development facilitates the accumulation of Tregs in neonatal skin and that upon skin entry these cells localize to HFs, a primary reservoir for skin commensals. Further, germ-free neonates had reduced skin Tregs indicating that commensal microbes augment Treg accumulation. We identified Ccl20 as a HF-derived, microbiota-dependent chemokine and found its receptor, Ccr6, to be preferentially expressed by Tregs in neonatal skin. The Ccl20-Ccr6 pathway mediated Treg migration in vitro and in vivo. Thus, HF morphogenesis, commensal microbe colonization, and local chemokine production work in concert to recruit Tregs into neonatal skin, thereby establishing this tissue Treg niche early in life.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by lung inflammation and high mortality rates. Lung cancer, specifically lung adenocarcinoma (LUAD), is a major cause of cancer-related deaths worldwide. Patients with LUAD, particularly those undergoing chemotherapy, are more likely to develop ARDS. ARDS inflicts major malfunctioning in the immune system. We suspected a certain shared pathogenic mechanism between these diseases. This study analyzed 503 LUAD patients from the TCGA-LUAD cohort as the training set, 85 LUAD cases from the GSE30219 cohort as the validation set, and 24 RNA-seq samples from ARDS mice model and control groups in the GSE2411 cohort. The differentially expressed genes (DEGs) of ARDS were analyzed using the limma package and screened by Cox and Lasso analysis. ssGSEA and xCell algorithms were utilized for immune landscaping. RT-qPCR analysis was used to determine the mRNA levels of key genes in both the LPS-induced ARDS model and human LUAD cell lines. We identified DEGs between ARDS and control groups, which were highly associated with cytokine production and leukocyte migration. A prognosis model for LUAD patients was developed based on the expressions of the key genes in the ARDS-derived DEGs, including FMO3, IL1R2, CCL20, CFTR, and GADD45G. A satisfactory efficacy was observed in both the training and validation cohorts. The model demonstrated increased effectiveness in predicting the intratumor immune profile and mutation status of LUAD. Moreover, we utilized LPS to induce the ARDS model, which resulted in elevated expressions of IL1R2 and CCL20. Additionally, CCL20 was upregulated in cancerous LUAD cell lines. We developed an ARDS-based model for stratifying LUAD prognosis. CCL20 was found to be elevated in both the ARDS model and LUAD, suggesting a shared underlying mechanism of these two diseases., (© 2024 Wiley Periodicals LLC.)

Small airway chronic inflammation is a major pathologic feature of chronic obstructive pulmonary disease (COPD) and is refractory to current treatments. Dendritic cells (DCs) accumulate around small airways in COPD. DCs are critical mediators of Ag surveillance and Ag presentation and amplify adaptive immune responses. How DCs accumulate around airways remains largely unknown. We use 2-photon DC imaging of living murine lung sections to directly visualize the dynamic movement of living DCs around airways in response to either soluble mediators (IL-1β) or environmental stimuli (cigarette smoke or TLR3 ligands) implicated in COPD pathogenesis. We find that DCs accumulate around murine airways primarily by increasing velocity (chemokinesis) rather than directional migration (chemotaxis) in response to all three stimuli. DC accumulation maximally occurs in a specific zone located 26-50 μm from small airways, which overlaps with zones of maximal DC velocity. Our data suggest that increased accumulation of DCs around airways results from increased numbers of highly chemokinetic DCs entering the lung from the circulation with balanced rates of immigration and emigration. Increases in DC accumulation and chemokinesis are partially dependent on ccr6, a crucial DC chemokine receptor, and fibroblast expression of the integrin αvβ8, a critical activator of TGF-β. αvβ8-Mediated TGF-β activation is known to enhance IL-1β-dependent fibroblast expression of the only known endogenous ccr6 chemokine ligand, ccl20. Taken together, these data suggest a mechanism by which αvβ8, ccl20, and ccr6 interact to lead to DC accumulation around airways in response to COPD-relevant stimuli.

CCL20 is the only chemokine ligand for the chemokine receptor CCR6, which is expressed by the critical antigen presenting cells, dendritic cells. Increased expression of CCL20 is likely involved in the increased recruitment of dendritic cells observed in fibroinflammatory diseases such as chronic obstructive pulmonary disease (COPD). CCL20 expression is increased by the proinflammatory cytokine IL-1β. We have determined that IL-1β-dependent CCL20 expression is also dependent on the multifunctional cytokine TGF-β. TGF-β is expressed in a latent form that must be activated to function, and activation is achieved through binding to the integrin αvβ8 (itgb8). Here we confirm correlative increases in αvβ8 and IL-1β with CCL20 protein in lung parenchymal lysates of a large cohort of COPD patients. How IL-1β- and αvβ8-mediated TGF-β activation conspire to increase fibroblast CCL20 expression remains unknown, because these pathways have not been shown to directly interact. We evaluate the 5'-flanking region of CCL20 to determine that IL-1β-driven CCL20 expression is dependent on αvβ8-mediated activation of TGF-β. We identify a TGF-β-responsive element (i.e. SMAD) located on an upstream enhancer of the human CCL20 promoter required for efficient IL-1β-dependent CCL20 expression. By chromatin immunoprecipitation, this upstream enhancer complexes with the p50 subunit of NF-κB on a NF-κB-binding element close to the transcriptional start site of CCL20. These interactions are confirmed by electromobility shift assays in nuclear extracts from human lung fibroblasts. These data define a mechanism by which αvβ8-dependent activation of TGF-β regulates IL-1β-dependent CCL20 expression in COPD.

Our gastrointestinal tract is a portal of entry for a number of bacteria and viruses. Thus, this tissue must develop ways to induce antigen-specific T cell and antibody responses quickly. Intestinal epithelial cells are a central player in barrier function and also in communicating signals from invading pathogens to the underlying immune tissue. Here we demonstrate that activation of Toll-like receptor 1 (TLR1) in the epithelium leads to the upregulation of the chemokine CCL20 during oral infection with Yersinia enterocolitica. Further, both neutralization of CCL20 using polyclonal antibody treatment and deletion of TLR1 resulted in a defect in CCR6+ dendritic cells (DCs), which produce innate cytokines that help to induce anti-Yersinia-specific T helper 17 (TH17) cells and IgA production. These data demonstrate a novel role for TLR1 signaling in the intestinal epithelium and demonstrate that together TLR1 and CCL20 are critical mediators of TH17 immunity through the activation and recruitment of DCs.

Although recent evidence indicates that several chemokines and defensins, well-known as inflammatory mediators, are expressed in the male and female reproductive tracts, the location and functional significance of chemokine networks in sperm physiology and sperm reproductive tract interactions are poorly understood. To address this deficiency in our knowledge, we examined the expression and function in sperm of CCR6, a receptor common to several chemoattractant peptides, and screened several reproductive tract fluids for the presence of specific ligands. CCR6 protein is present in mouse and human sperm and mainly localized in the sperm tail with other minor patterns in sperm from mice (neck and acrosomal region) and men (neck and midpiece regions). As expected from the protein immunoblotting and immunofluorescence results, mouse Ccr6 mRNA is expressed in the testis. Furthermore, the Defb29 mRNA encoding the CCR6 ligand, β-defensin DEFB29, is expressed at high levels in the epididymis. As determined by protein chip analysis, several chemokines (including some that act through CCR6, such as CCL20/MIP-3α (formerly macrophage inflammatory protein 3α) and protein hormones were present in human follicular fluid, endometrial secretions, and seminal plasma. In functional chemotaxis assays, capacitated human sperm exhibited a directional movement towards CCL20, and displayed modifications in motility parameters. Our data indicate that chemokine ligand/receptor interactions in the male and female genital tracts promote sperm motility and chemotaxis under non-inflammatory conditions. Therefore, some of the physiological reactions mediated by CCR6 ligands in male reproduction extend beyond a pro-inflammatory response and might find application in clinical reproduction and/or contraception.

M2-like tumor-associated macrophages (TAMs) are risk factors for cancer progression and metastasis. However, the mechanisms underlying their polarization are still not fully understood. Although cathepsin D (Cat D) has been reported as a procarcinogenic factor, little is known about the functional role of Cat D in the tumor microenvironment (TME). This study aimed to explore the effect and molecular mechanisms of Cat D in the TME. Cat D knockout (KO) altered the cytokine secretion pattern and induced TAM reprogramming from the M2 to M1 subtype, thereby preventing epithelial-mesenchymal transition and tumor metastasis. Mechanistically, we identified transforming growth factor beta-induced protein (TGFBI) as a Cat D target protein that is specifically associated with TAM polarization. Elevated TGFBI expression in Cat D KO cancer cells resulted in a decline in M2-like TAM polarization. Our RNA-sequencing results indicated that the cancer cell-secreted chemokine CCL20 is a major secretory chemokine for Cat D-TGFBI-mediated TAM polarization. In contrast, Cat D overexpression accelerated TAM polarization into M2-like cells by suppressing TGFBI expression. In addition, the double Cat D and TGFBI KO rescued the inhibitory effects of Cat D KO on tumor metastasis by controlling TAM and T-cell activation. These findings indicated that Cat D contributes to cancer metastasis through TGFBI-mediated TAM reprogramming. Cat D deletion inhibits M2-like TAM polarization through TGFBI-mediated CCL20 expression, reprogramming the immunosuppressive TME. Our results open a potential new avenue for therapy focused on eliminating tumor metastasis., (© 2024. The Author(s).)

Dendritic cells (DCs) form a network comprising different populations that initiate and differentially regulate immune responses. Langerhans cells (LCs) represent a unique population of DCs colonizing epithelium, and we present here observations suggesting that macrophage inflammatory protein (MIP)-3alpha plays a central role in LC precursor recruitment into the epithelium during inflammation. (a) Among DC populations, MIP-3alpha was the most potent chemokine inducing the selective migration of in vitro-generated CD34(+) hematopoietic progenitor cell-derived LC precursors and skin LCs in accordance with the restricted MIP-3alpha receptor (CC chemokine receptor 6) expression to these cells. (b) MIP-3alpha was mainly produced by epithelial cells, and the migration of LC precursors induced by the supernatant of activated skin keratinocytes was completely blocked with an antibody against MIP-3alpha. (c) In vivo, MIP-3alpha was selectively produced at sites of inflammation as illustrated in tonsils and lesional psoriatic skin where MIP-3alpha upregulation appeared associated with an increase in LC turnover. (d) Finally, the secretion of MIP-3alpha was strongly upregulated by cells of epithelial origin after inflammatory stimuli (interleukin 1beta plus tumor necrosis factor alpha) or T cell signals. Results of this study suggest a major role of MIP-3alpha in epithelial colonization by LCs under inflammatory conditions and immune disorders, and might open new ways to control epithelial immunity.

Rheumatoid arthritis (RA) is a type of arthritis autoimmune disease characterized by systemic chronic inflammation. C-C Chemokine ligand 20 (CCL20) is the same as most chemokines with immunomodulatory and inflammatory processes. The correlation of CCL20 in RA remains unclear. This study aimed to explore the association among levels of CCL20, T helper cell (TH) subset (Th1/Th2/Th17)-related cytokine levels, and clinical indices of RA disease activity. Serum CCL20 levels were quantified by enzyme-linked immunosorbent assay, and a flow-fluorescence technique was used to assess Th1/Th2/Th17-related cytokine levels. The serum CCL20 levels in patients were significantly higher than those in healthy controls and positively associated with C-reactive protein levels, erythrocyte sedimentation rate, and disease activity score-28 (DAS28). Patients with RA were categorized into 4 major groups, including remission, low, moderate, and high disease activity, with related DAS28 scores for each group. CCL20 levels of the disease moderate/high activity group were moderately positively correlated with IL-6 levels, but not with the other Th1/Th2/Th17-related cytokines. Serum CCL20 levels correlate strongly with RA disease activity and clinical inflammation and were significantly elevated in patients compared to healthy individuals. CCL20 plays a key role in the immune response of patients with RA and is, therefore, a potential biomarker of disease activity.

DCs (dendritic cells) function as sentinels of the immune system. They traffic from the blood to the tissues where, while immature, they capture antigens. They then leave the tissues and move to the draining lymphoid organs where, converted into mature DC, they prime naive T cells. This suggestive link between DC traffic pattern and functions led us to investigate the chemokine responsiveness of DCs during their development and maturation. DCs were differentiated either from CD34(+) hematopoietic progenitor cells (HPCs) cultured with granulocyte/macrophage colony-stimulating factor (GM-CSF) plus tumor necrosis factor (TNF)-alpha or from monocytes cultured with GM-CSF plus interleukin 4. Immature DCs derived from CD34(+) HPCs migrate most vigorously in response to macrophage inflammatory protein (MIP)-3alpha, but also to MIP-1alpha and RANTES (regulated on activation, normal T cell expressed and secreted). Upon maturation, induced by either TNF-alpha, lipopolysaccharide, or CD40L, DCs lose their response to these three chemokines when they acquire a sustained responsiveness to a single other chemokine, MIP-3beta. CC chemokine receptor (CCR)6 and CCR7 are the only known receptors for MIP-3alpha and MIP-3beta, respectively. The observation that CCR6 mRNA expression decreases progressively as DCs mature, whereas CCR7 mRNA expression is sharply upregulated, provides a likely explanation for the changes in chemokine responsiveness. Similarly, MIP-3beta responsiveness and CCR7 expression are induced upon maturation of monocyte- derived DCs. Furthermore, the chemotactic response to MIP-3beta is also acquired by CD11c+ DCs isolated from blood after spontaneous maturation. Finally, detection by in situ hybridization of MIP-3alpha mRNA only within inflamed epithelial crypts of tonsils, and of MIP-3beta mRNA specifically in T cell-rich areas, suggests a role for MIP-3alpha/CCR6 in recruitment of immature DCs at site of injury and for MIP-3beta/CCR7 in accumulation of antigen-loaded mature DCs in T cell-rich areas.

Introduction: Interleukin 17 (IL-17) and CC-chemokine ligand 20 (CCL20) are increasingly implicated in the pathogenesis of rheumatoid arthritis (RA). A correlation has been reported to exist between serum levels of IL-17 and CCL20 and the disease activity. However, such an effect has not been universally demonstrated. The aim of the present study was to investigate if serum levels of IL-17 and/or CCL20 reflect the disease activity and response to anti-TNF-α therapy in patients with RA. Material and methods: Twenty-two RA patients qualified to receive anti-TNF-α treatment were prospectively assessed before and after 12 weeks of therapy. Serum concentrations of IL-17 and CCL20 were measured with high-sensitivity immunoassays. Disease activity was assessed by the 28-joint disease activity score (DAS28). Results: Twelve weeks of therapy resulted in a satisfactory therapeutic response in the majority (91%) of patients (reflected both by clinical and standard biochemical criteria). However, serum concentrations of IL-17 and CCL20 did not change significantly over the course of therapy Moreover, they did not correlate with the disease activity, patient characteristics, and their response to therapy. Conclusions: Serum levels of IL-17 and CCL20 do not reflect changes in the clinical and biochemical status that occur in patients undergoing anti-TNF-α treatment for RA. The lack of such an association indicates that IL-17 signalling is not affected by anti-TNF-α therapy and is thus not critically involved in the disease pathogenesis. [ABSTRACT FROM AUTHOR]

The role of chemokines/receptors in the pathophysiological activities such as inflammation and tissue injury has been clarified. In recent years,there have been increasing studies on their effect on tumors in the tumor microenvironment. This article reviews research advances in C-C motif chemokine ligand 20(CCL20) and its receptor CCR6 in liver cancer and other tumors in recent years and analyzes the possible mechanism by which CCL20 and CCR6 promote tumor progression and their effect on tumor prognosis. Blocking CCL20/CCR6 interaction may provide a new direction for the targeted therapy for liver cancer. [ABSTRACT FROM AUTHOR]

Objective To investigate the serum levels of M30 and CCL20 and their association with short-term (3 -month) prognosis in patients with hepatitis B virus - related acute - on - chronic liver failure (HBV - ACLF) , as well as their clinical significance. Methods A total of 51 patients with HBV - ACLF who were diagnosed and treated in Hunan Provincial People's Hospital from October 2014 to January 2017 were enrolled as HBV - ACLF group; 30 patients with chronic hepatitis B (CUB) who were hospitalized or followed up in the outpatient service were enrolled as CHB group; 30 healthy individuals who underwent physical examination were enrolled as control group. The patients with HBV - ACLF were followed up for 3 months, and according to the results of follow - up, these patients were divided into survival group and death group. ELISA was used to measure the serum levels of M30 and CCL20 in peripheral blood before treatment and after two weeks of treatment. The t - test was used for comparison of continuous data between two groups, and an analysis of variance was used for comparison between multiple groups. Results There were significant differences in the serum levels of M30 and CCL20 before treatment between the HBV - ACLF group, the CUB group, and the control group ( M30; 591.54 ± 262. 06 U/L vs 241.58 ± 120. 33 U/L vs 114. 35 ± 52.09 U/L, F =22. 75.P <0.05; CCL20 : 386.51 ±55. 12 pg/ml vs 177. 11 ±27.51 pg/ml vs 33.95 ± 11.62 pg/ml, F=51.47,P< 0. 05 ). After two weeks of treatment, the HBV - ACLF (hath group had a significantly higher level of M30 than the HBV - ACLF survival group (648. 17 ±285.55 U/L vs 426.43 ±217.64 U/L, t = 2. 37, P <0.05 ) and a significantly lower level of CCL20 than the HBV-ACLFsurvival group (232. 28 ± 39. 28 pg/ml vs 352. 29 ±52.43 pg/ml. t = - 2. 35 . P <0. 05 ). After 2 weeks of treatment, there were significant differences in the change rates of the serum levels of M30 and CCL20 between the two groups ( M30: 0. 08 ±0. 04 vs 0. 27 ±0. 12 , t = 2. 49 . P <0. 05 ; CCL20: 0. 39 ±0. 06 vs 0. 11 ±0.02, t = 2. 54 , P <0. 05 ). Conclusion Patients with HBV - ACLF have significant increases in the serum levels of M30 and CCL20, which can accurately reflect cell apoptosis and inflammation in the liver. Patients with a significant reduction in CCL20 during treatment tend to have high mortality, and patients with a significant reduction in M30 tend to have good prognosis. Dynamic changes in M30 and CCL20 levels have a certain value in predicting the short - term prognosis of patients with HBV -ACLF [ABSTRACT FROM AUTHOR]