31 results on '"Amodio, Giada"'
Search Results
2. IL-10-producing regulatory cells impact on celiac disease evolution
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Passerini, Laura, Amodio, Giada, Bassi, Virginia, Vitale, Serena, Mottola, Ilaria, Di Stefano, Marina, Fanti, Lorella, Sgaramella, Paola, Ziparo, Chiara, Furio, Silvia, Auricchio, Renata, Barera, Graziano, Di Nardo, Giovanni, Troncone, Riccardo, Gianfrani, Carmen, and Gregori, Silvia
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- 2024
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3. Aging, inflammation and DNA damage in the somatic testicular niche with idiopathic germ cell aplasia
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Alfano, Massimo, Tascini, Anna Sofia, Pederzoli, Filippo, Locatelli, Irene, Nebuloni, Manuela, Giannese, Francesca, Garcia-Manteiga, Jose Manuel, Tonon, Giovanni, Amodio, Giada, Gregori, Silvia, Agresti, Alessandra, Montorsi, Francesco, and Salonia, Andrea
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- 2021
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4. Role of myeloid regulatory cells (MRCs) in maintaining tissue homeostasis and promoting tolerance in autoimmunity, inflammatory disease and transplantation
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Amodio, Giada, Cichy, Joanna, Conde, Patricia, Matteoli, Gianluca, Moreau, Aurélie, Ochando, Jordi, Oral, Barbaros H., Pekarova, Michaela, Ryan, Elizabeth J., Roth, Johannes, Sohrabi, Yahya, Cuturi, Maria-Cristina, and Gregori, Silvia
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- 2019
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5. DHRS9 is a Stable Marker of Human Regulatory Macrophages
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Bitterer, Florian, Amodio, Giada, Macedo, Camila, Moreau, Aurelie, Obermajer, Natasa, Frändrich, Fred, Cuturi, Cristina, Gregori, Silvia, Schlitt, Hans J., Thomson, Angus W., Geissler, Edward K., Hutchinson, James A., and Riquelme, Paloma
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- 2018
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6. DHRS9 Is a Stable Marker of Human Regulatory Macrophages
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Riquelme, Paloma, Amodio, Giada, Macedo, Camila, Moreau, Aurelie, Obermajer, Nataša, Brochhausen, Christoph, Ahrens, Norbert, Kekarainen, Tuija, Fändrich, Fred, Cuturi, Cristina, Gregori, Silvia, Metes, Diana, Schlitt, Hans J., Thomson, Angus W., Geissler, Edward K., and Hutchinson, James A.
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- 2017
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7. IL-10-Engineered Dendritic Cells Modulate Allogeneic CD8 + T Cell Responses.
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Fortunato, Marta, Amodio, Giada, and Gregori, Silvia
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CYTOTOXIC T cells , *T cells , *DENDRITIC cells , *CELL populations , *CD8 antigen , *GRAFT versus host disease , *HOMEOSTASIS - Abstract
Tolerogenic dendritic cells (tolDC) play a central role in regulating immune homeostasis and in promoting peripheral tolerance. These features render tolDC a promising tool for cell-based approaches aimed at inducing tolerance in T-cell mediated diseases and in allogeneic transplantation. We developed a protocol to generate genetically engineered human tolDC overexpressing IL-10 (DCIL-10) by means of a bidirectional lentiviral vector (LV) encoding for IL-10. DCIL-10 promote allo-specific T regulatory type 1 (Tr1) cells, modulate allogeneic CD4+ T cell responses in vitro and in vivo, and are stable in a pro-inflammatory milieu. In the present study, we investigated the ability of DCIL-10 to modulate cytotoxic CD8+ T cell responses. We demonstrate that DCIL-10 reduces allogeneic CD8+ T cell proliferation and activation in primary mixed lymphocyte reactions (MLR). Moreover, long-term stimulation with DCIL-10 induces allo-specific anergic CD8+ T cells without signs of exhaustion. DCIL-10-primed CD8+ T cells display limited cytotoxic activity. These findings indicate that stable over-expression of IL-10 in human DC leads to a population of cells able to modulate cytotoxic allogeneic CD8+ T cell responses, overall indicating that DCIL-10 represent a promising cellular product for clinical applications aimed at inducing tolerance after transplantation. [ABSTRACT FROM AUTHOR]
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- 2023
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8. Dendritic Cell Immune Therapy to Break or Induce Tolerance
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Amodio, Giada, Annoni, Andrea, and Gregori, Silvia
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- 2015
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9. Combined plasma levels of IL‐10 and testosterone, but not soluble HLA‐G5, predict the risk of death in COVID‐19 patients.
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Amodio, Giada, Capogrosso, Paolo, Pontillo, Marina, Tassara, Michela, Boeri, Luca, Carenzi, Cristina, Cignoli, Daniele, Ferrara, Anna Maria, Ramirez, Giuseppe A., Tresoldi, Cristina, Locatelli, Massimo, Santoleri, Luca, Castagna, Antonella, Zangrillo, Alberto, De Cobelli, Francesco, Tresoldi, Moreno, Landoni, Giovanni, Rovere‐Querini, Patrizia, Ciceri, Fabio, and Montorsi, Francesco
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SARS-CoV-2 , *COVID-19 , *CORONAVIRUS diseases , *INTERLEUKIN-10 - Abstract
Background: The identification of biomarkers correlated with coronavirus disease 2019 (COVID‐19) outcomes is a relevant need for clinical management. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is characterized by elevated interleukin (IL)‐6, IL‐10, HLA‐G, and impaired testosterone production. Objectives: We aimed at defining the combined impact of sex hormones, interleukin‐10, and HLA‐G on COVID‐19 pathophysiology and their relationship in male patients. Materials and methods: We measured by chemiluminescence immunoassay, electrochemiluminescent assays, and enzyme‐linked immunosorbent assay circulating total testosterone, 17β‐estradiol (E2), IL‐10, and ‐HLAG5 as well as SARS‐CoV‐2 S1/S2 Immunoglobulin G from 292 healthy controls and 111 COVID‐19 patients with different disease severity at hospital admission, and in 53 COVID‐19 patients at 7‐month follow‐up. Results and discussion: We found significantly higher levels of IL‐10, HLA‐G, and E2 in COVID‐19 patients compared to healthy controls and an inverse correlation between IL‐10 and testosterone, with IL‐10, progressively increasing and testosterone progressively decreasing with disease severity. This correlation was lost at the 7‐month follow‐up. The risk of death in COVID‐19 patients with low testosterone increased in the presence of high IL‐10. A negative correlation between SARS‐CoV‐2 Immunoglobulin G and HLA‐G or IL‐10 at hospitalization was observed. At the 7‐month follow‐up, IL‐10 and testosterone normalized, and HLA‐G decreased. Conclusion: Our findings indicate that combined evaluation of IL‐10 and testosterone predicts the risk of death in men with COVID‐19 and support the hypothesis that IL‐10 fails to suppress excessive inflammation by promoting viral spreading. [ABSTRACT FROM AUTHOR]
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- 2023
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10. Natural history of type 1 diabetes on an immunodysregulatory background with genetic alteration in B-cell activating factor receptor: A case report.
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Di Lorenzo, Biagio, Pacillo, Lucia, Milardi, Giulia, Jofra, Tatiana, Di Cesare, Silvia, Gerosa, Jolanda, Marzinotto, Ilaria, Zapparoli, Ettore, Rivalta, Beatrice, Cifaldi, Cristina, Barzaghi, Federica, Giancotta, Carmela, Zangari, Paola, Rapini, Novella, Deodati, Annalisa, Amodio, Giada, Passerini, Laura, Carrera, Paola, Gregori, Silvia, and Palma, Paolo
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TALL-1 (Protein) ,TYPE 1 diabetes ,NATURAL history ,LOW-carbohydrate diet ,COMMON variable immunodeficiency ,POLYNEUROPATHIES ,AGAMMAGLOBULINEMIA - Abstract
The immunological events leading to type 1 diabetes (T1D) are complex and heterogeneous, underscoring the necessity to study rare cases to improve our understanding. Here, we report the case of a 16-year-old patient who showed glycosuria during a regular checkup. Upon further evaluation, stage 2 T1D, autoimmune thrombocytopenic purpura (AITP), and common variable immunodeficiency (CVID) were diagnosed. The patient underwent low carb diet, losing > 8 kg, and was placed on Ig replacement therapy. Anti-CD20 monoclonal antibody (Rituximab, RTX) was administered 2 years after diagnosis to treat peripheral polyneuropathy, whereas an atypical mycobacteriosis manifested 4 years after diagnosis and was managed with prolonged antibiotic treatment. In the fifth year of monitoring, the patient progressed to insulin dependency despite ZnT8A autoantibody resolution and IA-2A and GADA autoantibody decline. The patient had low T1D genetic risk score (GRS = 0.22817) and absence of human leukocyte antigen (HLA) DR3/DR4-DQ8. Genetic analysis identified the monoallelic mutation H159Y in TNFRSF13C, a gene encoding B-cell activating factor receptor (BAFFR). Significant reduced blood B-cell numbers and BAFFR levels were observed in line with a dysregulation in BAFF-BAFFR signaling. The elevated frequency of PD-1+ dysfunctional Tfh cells composed predominantly by Th1 phenotype was observed at disease onset and during follow-up. This case report describes a patient progressing to T1D on a BAFFR-mediated immunodysregulatory background, suggesting a role of BAFF-BAFFR signaling in islet-specific tolerance and T1D progression. [ABSTRACT FROM AUTHOR]
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- 2022
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11. Alteration of interleukin-10-producing Type 1 regulatory cells in autoimmune diseases.
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Gregori, Silvia, Amodio, Giada, Passerini, Laura, and Santoni de Sio, Francesca Romana
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- 2022
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12. Altered Frequency and Phenotype of HLA-G-Expressing DC-10 in Type 1 Diabetes Patients at Onset and in Subjects at Risk to Develop the Disease.
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Amodio, Giada, Mandelli, Alessandra, Curto, Rosalia, Rancoita, Paola M. V., Stabilini, Angela, Bonfanti, Riccardo, de Pellegrin, Maurizio, Bosi, Emanuele, Di Serio, Clelia, Battaglia, Manuela, and Gregori, Silvia
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TYPE 1 diabetes ,AUTOIMMUNE diseases ,PEOPLE with diabetes ,PROGNOSIS ,PHENOTYPES ,MULTIPLE regression analysis - Abstract
Type 1 diabetes (T1D) is a chronic autoimmune disease resulting in progressive destruction of β-cells. Several factors affecting lymphocyte and antigen-presenting cells, including dendritic cells (DCs), contribute to defective maintenance of tolerance in T1D. DC-10 are a subset of human DCs involved in IL-10-mediated tolerance. A precise monitoring of DC-10 in the peripheral blood is possible thanks to the discovery of specific biomarkers. DC-10, being cells that naturally express HLA-G, may be used for the appropriate staging of the disease. By enumerating and phenotypically characterizing DC-10 in the peripheral blood of subjects at different stages of T1D development—first-degree relatives (FDRs) of T1D patients, without (Ab
neg ) or with (Abpos ) autoantibodies, T1D patients at onset, and age-matched healthy controls (HCs)—we showed that DC-10 contain a high proportion of HLA-G-expressing cells as compared with monocytes. We reported that a low frequency of DC-10 during disease development is paralleled with the increased proportion of pro-inflammatory cDC2 cells. Moreover, DC-10 number and phenotype differ from Abneg FDRs, Abpos FDRs, and T1D patients compared with HCs, and DC-10 from T1D patients express low levels of CD83. Finally, multiple regression analysis, considering DC-10 and HLA-G-related parameters, showed that Abneg FDRs are more similar to subjects with autoimmunity than to HCs. This is the first demonstration that impairment in DC-10 number and phenotype, specifically CD83 expression, is associated with risk of developing T1D, suggesting a possible use of CD83+ DC-10 to stratify individuals at risk of T1D in conjunction with classical prognostic factors. [ABSTRACT FROM AUTHOR]- Published
- 2021
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13. Inhibition of iNKT Cells by the HLA-G-ILT2 Checkpoint and Poor Stimulation by HLA-G-Expressing Tolerogenic DC.
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Wu, Ching-Lien, Caumartin, Julien, Amodio, Giada, Anna, François, Loustau, Maria, Gregori, Silvia, Langlade-Demoyen, Pierre, and LeMaoult, Joel
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GLYCOLIPIDS ,HISTOCOMPATIBILITY antigens ,CYTOTOXIC T cells ,CELL populations ,CELL physiology ,KILLER cells ,CELLS ,KILLER cell receptors ,SECRETION - Abstract
Invariant Natural Killer T (iNKT) cells are a small and distinct population of T cells crucial in immunomodulation. After activation by alpha-GalactosylCeramide (αGC), an exogenic glycolipid antigen, iNKT cells can rapidly release cytokines to enhance specific anti-tumor activity. Several human clinical trials on iNKT cell-based anti-cancer are ongoing, however results are not as striking as in murine models. Given that iNKT-based immunotherapies are dependent mainly on antigen-presenting cells (APC), a human tolerogenic molecule with no murine homolog, such as Human Leucocyte Antigen G (HLA-G), could contribute to this discrepancy. HLA-G is a well-known immune checkpoint molecule involved in fetal-maternal tolerance and in tumor immune escape. HLA-G exerts its immunomodulatory functions through the interaction with immune inhibitory receptors such as ILT2, differentially expressed on immune cell subsets. We hypothesized that HLA-G might inhibit iNKT function directly or by inducing tolerogenic APC leading to iNKT cell anergy, which could impact the results of current clinical trials. Using an ILT2-transduced murine iNKT cell line and human iNKT cells, we demonstrate that iNKT cells are sensitive to HLA-G, which inhibits their cytokine secretion. Furthermore, human HLA-G
+ dendritic cells, called DC-10, failed at inducing iNKT cell activation compared to their autologous HLA-G‒ DCs counterparts. Our data show for the first time that the HLA-G/ILT2 ICP is involved in iNKT cell function modulation. [ABSTRACT FROM AUTHOR]- Published
- 2021
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14. HLA-G Genotype/Expression/Disease Association Studies: Success, Hurdles, and Perspectives.
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Amodio, Giada and Gregori, Silvia
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DISEASE susceptibility ,GENOTYPES ,BODY fluids ,DISEASE progression ,PROTEIN expression ,AMPLIFIED fragment length polymorphism - Abstract
The non-classical HLA-G is a well-known immune-modulatory molecule. In physiological condition, HLA-G surface expression is restricted to the maternal–fetal interface and to immune-privileged adult tissues, whereas soluble forms of HLA-G are detectable in various body fluids. HLA-G can be de novo expressed in pathological conditions including tumors, chronic infections, or after allogeneic transplantation. HLA-G exerts positive effects modulating innate and adaptive immune responses and promoting tolerance, or detrimental effects inducing immune escape mechanisms. HLA-G locus, in contrast to classical HLA class I gene, is highly polymorphic in the non-coding 3′ untranslated region (UTR) and in the 5′ upstream regulatory region (5′ URR). Variability in these regions influences HLA-G expression by modifying mRNA stability or allowing posttranscriptional regulation in the case of 3′ UTR or by sensing the microenvironment and responding to specific stimuli in the case of HLA-G promoter regions (5′ URR). The influence of genetic variations on the expression of HLA-G makes it an attractive biomarker to monitor disease predisposition and progression, or response to therapy. Here, we summarize the current knowledge, efforts, and obstacles to generate a general consensus on the correlation between HLA-G genetic variability, protein expression, and disease predisposition. Moreover, we discuss perspectives for future investigation on HLA-G genotype/expression in association with disease predisposition and progression. [ABSTRACT FROM AUTHOR]
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- 2020
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15. Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer.
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Comi, Michela, Amodio, Giada, Passeri, Laura, Fortunato, Marta, Santoni de Sio, Francesca Romana, Andolfi, Grazia, Kajaste-Rudnitski, Anna, Russo, Fabio, Cesana, Luca, and Gregori, Silvia
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DENDRITIC cells ,GENETIC transformation ,SUPPRESSOR cells ,T cells ,MOUSE diseases - Abstract
The prominent role of dendritic cells (DC) in promoting tolerance and the development of methods to generate clinical grade products allowed the clinical application of tolerogenic DC (tolDC)-based therapies for controlling unwanted immune responses. We established an efficient method to generate tolerogenic human DC, producing supra-physiological levels of IL-10, by genetically engineering monocyte-derived DC with a bidirectional Lentiviral Vector (bdLV) encoding for IL-10 and a marker gene. DC
IL−10 are mature DC, modulate T cell responses, promote T regulatory cells, and are phenotypically and functionally stable upon stimulation. Adoptive transfer of human DCIL−10 in a humanized mouse model dampens allogeneic T cell recall responses, while murine DCIL−10 delays acute graft-vs.-host disease in mice. Our report outlines an efficient method to transduce human myeloid cells with large-size LV and shows that stable over-expression of IL-10 generates an effective cell product for future clinical applications in the contest of allogeneic transplantation. [ABSTRACT FROM AUTHOR]- Published
- 2020
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16. Interleukin-10-Producing DC-10 Is a Unique Tool to Promote Tolerance Via Antigen-Specific T Regulatory Type 1 Cells.
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Comi, Michela, Amodio, Giada, and Gregori, Silvia
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INTERLEUKIN-10 ,T cells - Abstract
The prominent role of tolerogenic dendritic cells (tolDCs) in promoting immune tolerance and the development of efficient methods to generate clinical grade products allow the application of tolDCs as cell-based approach to dampen antigen (Ag)-specific T cell responses in autoimmunity and transplantation. Interleukin (IL)-10 potently modulates the differentiation and functions of myeloid cells. Our group contributed to the identification of IL-10 as key factor in inducing a subset of human tolDCs, named dendritic cell (DC)-10, endowed with the ability to spontaneously release IL-10 and induce Ag-specific T regulatory type 1 (Tr1) cells. We will provide an overview on the role of IL-10 in modulating myeloid cells and in promoting DC-10. Moreover, we will discuss the clinical application of DC-10 as inducers of Ag-specific Tr1 cells for tailoring Tr1-based cell therapy, and as cell product for promoting and restoring tolerance in T-cell-mediated diseases. [ABSTRACT FROM AUTHOR]
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- 2018
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17. Association of genetic variants in the 3′UTR of HLA-G with Recurrent Pregnancy Loss.
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Amodio, Giada, Canti, Valentina, Maggio, Luana, Rosa, Susanna, Castiglioni, Maria Teresa, Rovere-Querini, Patrizia, and Gregori, Silvia
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HUMAN genetic variation , *HLA histocompatibility antigens , *RECURRENT miscarriage , *IMMUNE response , *PREGNANCY complications - Abstract
Human Leukocyte Antigen (HLA)-G is involved in reprogramming immune responses at fetal-maternal interface during pregnancy. We evaluated the genetic diversity of the 3′ Un-Translated Region (UTR) of HLA-G , previously associated with HLA-G mRNA post-transcriptional regulation, in women with unexplained Recurrent Pregnancy Loss (RPL), with 2 pregnancy losses (RPL-2, n = 28), or 3 or more pregnancy losses (RPL-3, n = 24), and in 30 women with a history of successful pregnancy. Results showed in RPL-2, but not in RPL-3, women compared to controls: i) higher frequency of the 14 bp Ins allele, in single and in double copy; ii) significantly lower frequency of DelG/X genotype, iii) reduced frequency of the UTR-2, and UTR-3 haplotypes; iv) higher frequencies of the UTR-5, UTR-7, and UTR-8 haplotypes. This pilot study supports the relevance of performing 3′UTR HLA-G genetic screening, not limited to a specific polymorphism, but considering the extended haplotypes, as a possible predictor of pregnancy outcome. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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18. HLA-G orchestrates the early interaction of human trophoblasts with the maternal.
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Gregori, Silvia, Amodio, Giada, Quattrone, Federica, and Panina-Bordignon2, Paola
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LEUCOCYTES ,TROPHOBLAST ,MATERNAL-fetal exchange ,HLA histocompatibility antigens ,STROMAL cells ,ENDOTHELIAL cells ,DENDRITIC cells ,VASCULAR remodeling - Abstract
Extravillous trophoblasts (EVTs) play a central role in educating maternal leukocytes, endometrial stromal and endothelial cells to generate a receptive decidual microenvironment tailored to accept the semi-allogeneic fetus. HLA-G, a non-classical HLA class I molecule endowed with immune-regulatory functions, is primarily expressed on EVTs lining the placenta and on the naturally occurring tolerogenic dendritic cells, named DC- 10, which are enriched in the human first trimester decidua. Decidual DC-10 are involved in HLA-G-mediated tolerance at the maternal-fetal interface. EVTs not only establish a tolerogenic microenvironment through the interaction with maternal innate and adaptive cells but also orchestrate placenta vascular and tissue remodeling, leading to a successful pregnancy. Here, we discuss the potential implications of the HLA-G-mediated cross-talk among the cells present at the maternal-fetal interface, and its role in maintaining a positive relationship between the mother and the fetus. [ABSTRACT FROM AUTHOR]
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- 2015
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19. HLA-G Expression on Blasts and Tolerogenic Cells in Patients Affected by Acute Myeloid Leukemia.
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Locafaro, Grazia, Amodio, Giada, Tomasoni, Daniela, Tresoldi, Cristina, Ciceri, Fabio, and Gregori, Silvia
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HLA histocompatibility antigens , *CANCER cells , *CELLULAR immunity , *ANTINEOPLASTIC agents , *ACUTE myeloid leukemia , *DENDRITIC cells - Abstract
Human Leukocyte Antigen-G (HLA-G) contributes to cancer cell immune escape from host antitumor responses. The clinical relevance of HLA-G in several malignancies has been reported. However, the role of HLA-G expression and functions in Acute Myeloid Leukemia (AML) is still controversial. Our group identified a subset of tolerogenic dendritic cells, DC-10 that express HLA-G and secrete IL-10. DC-10 are present in the peripheral blood and are essential in promoting and maintaining tolerance via the induction of adaptive T regulatory (Treg) cells. We investigated HLA-G expression on blasts and the presence of HLA-G-expressing DC-10 and CD4+ T cells in the peripheral blood of AML patients at diagnosis. Moreover, we explored the possible influence of the 3' untranslated region (3'UTR) of HLA-G, which has been associated with HLA-G expression, on AML susceptibility. Results showed that HLA-G-expressing DC-10 and CD4+ T cells are highly represented in AML patients with HLA-G positive blasts. None of the HLA-G variation sites evaluated was associated with AML susceptibility. This is the first report describing HLA-G-expressing DC-10 and CD4+ T cells in AML patients, suggesting that they may represent a strategy by which leukemic cells escape the host's immune system. Further studies on larger populations are required to verify our findings. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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20. Corrigendum: Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer.
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Comi, Michela, Amodio, Giada, Passeri, Laura, Fortunato, Marta, Santoni de Sio, Francesca Romana, Andolfi, Grazia, Kajaste-Rudnitski, Anna, Russo, Fabio, Cesana, Luca, and Gregori, Silvia
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DENDRITIC cells ,GENETIC transformation ,LABORATORY mice ,IMMUNOLOGICAL tolerance ,CELLULAR therapy - Abstract
Keywords: dendritic cells; IL-10; cell therapy; immune tolerance; allogeneic transplantation EN dendritic cells IL-10 cell therapy immune tolerance allogeneic transplantation N.PAG N.PAG 2 03/24/21 20210322 NES 210322 In the original article, there was a mistake: a duplication of one dot plot in Figure 8B as published. Dendritic cells, IL-10, cell therapy, immune tolerance, allogeneic transplantation Female Balb/c BM cells were differentiated into DC, transduced at day 2 with LV-GFP (DC GFP) or LV-IL-10 (DC IL-10), and activated with LPS (200 ng/ml) during the last 2 days of differentiation. [Extracted from the article]
- Published
- 2021
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21. HLA-G expressing DC-10 and CD4+ T cells accumulate in human decidua during pregnancy.
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Amodio, Giada, Mugione, Alessandra, Sanchez, Ana Maria, Viganò, Paola, Candiani, Massimo, Somigliana, Edgardo, Roncarolo, Maria Grazia, Panina-Bordignon, Paola, and Gregori, Silvia
- Subjects
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HLA histocompatibility antigens , *CD4 antigen , *T cells , *GENE expression , *BIOACCUMULATION , *DURATION of pregnancy , *IMMUNE response - Abstract
Abstract: Multiple mechanisms underlie the surprising willingness of mothers to tolerate the semi-allogeneic fetal tissues during pregnancy. Chief among these is the expression of the HLA-G molecules that has been largely demonstrated to be responsible for reprogramming the local maternal immune response towards tolerance. We recently identified a subset of tolerogenic dendritic cells, DC-10 that secrete high amounts of IL-10 and express high levels of HLA-G and its ligand ILT4. DC-10 are present in the peripheral blood and are essential in inducing adaptive regulatory T cells. We investigated the presence of DC-10 and HLA-G-expressing CD4+ T cells in human decidua in the first trimester of pregnancy. Results showed that these cells are highly represented in human decidua as compared to the peripheral blood. This is the first report describing decidual DC-10 and CD4+HLA-G+ T cells, strongly suggesting that they may accumulate or be induced at the fetal maternal interface to promote tolerance. [Copyright &y& Elsevier]
- Published
- 2013
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22. Dendritic cells: a double-dge sword in autoimmune responses.
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Amodio, Giada and Gregori, Silvia
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DENDRITIC cells ,AUTOIMMUNE diseases ,IMMUNE response ,ANTIGEN presenting cells ,LYMPHOID tissue - Abstract
Dendritic cells (DC) are antigen-presenting cells that play a pivotal role in regulating innate and adaptive immune responses. In autoimmunity, DC act as a double-edged sword since on one hand they initiate adaptive self-reactive responses and on the other they play a pivotal role in promoting and maintaining tolerance. Thus, DC are the most important cells in either triggering self-specific responses or in negatively regulating auto-reactive responses. The latter function is mediated by DC in the steady-state or specialized subsets of DC, named tolerogenic DC. Clinical and experimental evidence indicate that prolonged presentation of self-antigens by DC is crucial for the development of destructive autoimmune diseases, and defects in tolerogenic DC functions contribute to eradication of self-tolerance. In recent years, DC have emerged as therapeutic targets for limiting their immunogenicity against self-antigens, while tolerogenic DC have been conceived as therapeutic tools to restore tolerance. The purpose of this review is to give a general overview of the current knowledge on the pathogenic role of DC in patients affected by autoimmune diseases. In addition, the protective role of tolerogenic DC will be addressed. The currently applied strategies to block immune activation or to exploit the tolerogenic potential of DC will be discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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23. F.58. Î3-chain Provides a Spontaneous and GH-dependent Signal for Cell Cycle Progression Related to its Cellular Amount
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Amorosi, Stefania, Russo, Ilaria, Amodio, Giada, Garbi, Corrado, Vitiello, Laura, Palamaro, Loredana, Vigliano, Ilaria, and Pignata, Claudio
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- 2008
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24. Protocol to assess the suppression of T-cell proliferation by human MDSC.
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Bruger AM, Vanhaver C, Bruderek K, Amodio G, Tavukçuoğlu E, Esendagli G, Gregori S, Brandau S, and van der Bruggen P
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- Cell Separation methods, Humans, Lymphocyte Activation, Myeloid-Derived Suppressor Cells cytology, Staining and Labeling methods, T-Lymphocytes cytology, Cell Proliferation, Coculture Techniques methods, Myeloid-Derived Suppressor Cells immunology, T-Lymphocytes immunology
- Abstract
Inhibition of T-cell proliferation is the most common approach to assess human myeloid-derived suppressor cell (MDSC) functions. However, diverse methodologies hinder the comparison of results obtained in different laboratories. In this chapter, we present a T-cell proliferation assay procedure based on allogeneic MDSC and T-cells that is potentially suitable to multi-center studies. The T-cells are isolated from non-cancerous donors and frozen for later use in different research groups. We observed that pure thawed T-cells showed poor proliferative capacities. To retain proliferation, T-cell-autologous mature dendritic cells are supplemented after thawing. MDSC are isolated from clinical samples and represent the sole variant between assays. Flow cytometry is used to assess T-cell proliferation by the dilution of a tracking dye., (© 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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25. The discovery of HLA-G-bearing extracellular vesicles: new perspectives in HLA-G biology.
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Amodio G and Gregori S
- Abstract
Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.
- Published
- 2017
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26. HLA-G expression levels influence the tolerogenic activity of human DC-10.
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Amodio G, Comi M, Tomasoni D, Gianolini ME, Rizzo R, LeMaoult J, Roncarolo MG, and Gregori S
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- 3' Untranslated Regions, Alleles, Cell Differentiation, Clonal Anergy genetics, Clonal Anergy immunology, Cytokines biosynthesis, Dendritic Cells cytology, Gene Frequency, Genotype, HLA-G Antigens metabolism, Humans, Immunophenotyping, Membrane Glycoproteins genetics, Membrane Glycoproteins metabolism, MicroRNAs genetics, T-Lymphocyte Subsets cytology, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, Dendritic Cells immunology, Dendritic Cells metabolism, Gene Expression, HLA-G Antigens genetics, Immune Tolerance genetics
- Abstract
Human leukocyte antigen (HLA)-G is a non-classical HLA class I molecule with known immune-modulatory functions. Our group identified a subset of human dendritic cells, named DC-10, that induce adaptive interleukin-10-producing T regulatory type 1 (Tr1) cells via the interleukin-10-dependent HLA-G/ILT4 pathway. In this study we aimed at defining the role of HLA-G in DC-10-mediated Tr1 cell differentiation. We analyzed phenotype, functions, and genetic variations in the 3' untranslated region of the HLA-G locus of in vitro-differentiated DC-10 from 67 healthy donors. We showed that HLA-G expression on DC-10 is donor-dependent. Functional studies demonstrated that DC-10, independently of HLA-G expression, secrete interleukin-10 and negligible levels of interleukin-12. Interestingly, DC-10 with high HLA-G promote allo-specific anergic T cells that contain a significantly higher frequency of Tr1 cells, defined as interleukin-10-producing (P=0.0121) or CD49b(+)LAG-3(+) (P=0.0031) T cells, compared to DC-10 with low HLA-G. We found that the HLA-G expression on DC-10 is genetically imprinted, being associated with specific variations in the 3' untranslated region of the gene, and it may be finely tuned by microRNA-mediated post-transcriptional regulation. These data highlight the important role of HLA-G in boosting DC-10 tolerogenic activity and confirm that interleukin-10 production by DC-10 is necessary but not sufficient to promote Tr1 cells at high frequency. These new insights into the role of HLA-G in DC-10-mediated induction of Tr1 cells provide additional information for clinical use in Tr1- or DC-10-based cell therapy approaches., (Copyright© Ferrata Storti Foundation.)
- Published
- 2015
- Full Text
- View/download PDF
27. HLA-G expressing DC-10 and CD4(+) T cells accumulate in human decidua during pregnancy.
- Author
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Amodio G, Mugione A, Sanchez AM, Viganò P, Candiani M, Somigliana E, Roncarolo MG, Panina-Bordignon P, and Gregori S
- Subjects
- Antigens, CD genetics, Antigens, CD immunology, Antigens, CD1, Antigens, Surface genetics, Antigens, Surface immunology, Cell Adhesion Molecules genetics, Cell Adhesion Molecules immunology, Decidua cytology, Dendritic Cells cytology, Female, Fetus, Glycoproteins, HLA-G Antigens genetics, Histocompatibility, Maternal-Fetal, Humans, Immunophenotyping, Interleukin-10 genetics, Lectins, C-Type genetics, Lectins, C-Type immunology, Pregnancy, Pregnancy Trimester, First, Receptors, Cell Surface genetics, Receptors, Cell Surface immunology, T-Lymphocytes, Regulatory cytology, Decidua immunology, Dendritic Cells immunology, Gene Expression immunology, HLA-G Antigens immunology, Immune Tolerance genetics, Interleukin-10 immunology, T-Lymphocytes, Regulatory immunology
- Abstract
Multiple mechanisms underlie the surprising willingness of mothers to tolerate the semi-allogeneic fetal tissues during pregnancy. Chief among these is the expression of the HLA-G molecules that has been largely demonstrated to be responsible for reprogramming the local maternal immune response towards tolerance. We recently identified a subset of tolerogenic dendritic cells, DC-10 that secrete high amounts of IL-10 and express high levels of HLA-G and its ligand ILT4. DC-10 are present in the peripheral blood and are essential in inducing adaptive regulatory T cells. We investigated the presence of DC-10 and HLA-G-expressing CD4(+) T cells in human decidua in the first trimester of pregnancy. Results showed that these cells are highly represented in human decidua as compared to the peripheral blood. This is the first report describing decidual DC-10 and CD4(+)HLA-G(+) T cells, strongly suggesting that they may accumulate or be induced at the fetal maternal interface to promote tolerance., (Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
28. Human tolerogenic DC-10: perspectives for clinical applications.
- Author
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Amodio G and Gregori S
- Abstract
Dendritic cells (DCs) are critically involved in inducing either immunity or tolerance. During the last decades efforts have been devoted to the development of ad hoc methods to manipulate DCs in vitro to enhance or stabilize their tolerogenic properties. Addition of IL-10 during monocyte-derived DC differentiation allows the induction of DC-10, a subset of human tolerogenic DCs characterized by high IL-10/IL-12 ratio and co-expression of high levels of the tolerogenic molecules HLA-G and immunoglobulin-like transcript 4. DC-10 are potent inducers of adaptive type 1 regulatory T cells, well known to promote and maintain peripheral tolerance. In this review we provide an in-depth comparison of the phenotype and mechanisms of suppression mediated by DC-10 and other known regulatory antigen-presenting cells currently under clinical development. We discuss the clinical therapeutic application of DC-10 as inducers of type 1 regulatory T cells for tailoring regulatory T-cell-based cell therapy, and the use of DC-10 as adoptive cell therapy for promoting and restoring tolerance in T-cell-mediated diseases.
- Published
- 2012
- Full Text
- View/download PDF
29. Dendritic cells a double-edge sword in autoimmune responses.
- Author
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Amodio G and Gregori S
- Abstract
Dendritic cells (DC) are antigen-presenting cells that play a pivotal role in regulating innate and adaptive immune responses. In autoimmunity, DC act as a double-edged sword since on one hand they initiate adaptive self-reactive responses and on the other they play a pivotal role in promoting and maintaining tolerance. Thus, DC are the most important cells in either triggering self-specific responses or in negatively regulating auto-reactive responses. The latter function is mediated by DC in the steady-state or specialized subsets of DC, named tolerogenic DC. Clinical and experimental evidence indicate that prolonged presentation of self-antigens by DC is crucial for the development of destructive autoimmune diseases, and defects in tolerogenic DC functions contribute to eradication of self-tolerance. In recent years, DC have emerged as therapeutic targets for limiting their immunogenicity against self-antigens, while tolerogenic DC have been conceived as therapeutic tools to restore tolerance. The purpose of this review is to give a general overview of the current knowledge on the pathogenic role of DC in patients affected by autoimmune diseases. In addition, the protective role of tolerogenic DC will be addressed. The currently applied strategies to block immune activation or to exploit the tolerogenic potential of DC will be discussed.
- Published
- 2012
- Full Text
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30. The cellular amount of the common gamma-chain influences spontaneous or induced cell proliferation.
- Author
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Amorosi S, Russo I, Amodio G, Garbi C, Vitiello L, Palamaro L, Adriani M, Vigliano I, and Pignata C
- Subjects
- B-Lymphocytes enzymology, B-Lymphocytes pathology, Cell Cycle genetics, Cell Cycle immunology, Cell Line, Transformed, Cells, Cultured, Dose-Response Relationship, Immunologic, Gene Knockdown Techniques, Growth Substances genetics, Growth Substances physiology, Humans, Interleukin Receptor Common gamma Subunit antagonists & inhibitors, Interleukin Receptor Common gamma Subunit deficiency, Interleukin Receptor Common gamma Subunit genetics, Janus Kinase 3 antagonists & inhibitors, Janus Kinase 3 genetics, Janus Kinase 3 metabolism, Lymphocyte Activation genetics, Lymphocyte Count, RNA, Small Interfering genetics, X-Linked Combined Immunodeficiency Diseases immunology, X-Linked Combined Immunodeficiency Diseases metabolism, X-Linked Combined Immunodeficiency Diseases pathology, B-Lymphocytes immunology, B-Lymphocytes metabolism, Cell Proliferation, Interleukin Receptor Common gamma Subunit biosynthesis, Lymphocyte Activation immunology
- Abstract
Mutations of the IL2RG encoding the common gamma-chain (gamma(c)) lead to the X-linked SCID disease. Gene correction through ex vivo retroviral transduction restored the immunological impairment in the most of treated patients, although lymphoproliferative events occurred in five of them. Even though in two cases it was clearly documented an insertional mutagenesis in LMO2, it is conceivable that gamma(c) could have a role per se in malignant lymphoproliferation. The gamma(c) is a shared cytokine receptor subunit, involved also in growth hormone (GH) receptor signaling. Through short interfering RNA or using X-linked SCID B lymphoblastoid cell lines lacking gamma(c), we demonstrate that self-sufficient growth was strongly dependent on gamma(c) expression. Furthermore, a correlation between gamma(c) amount and the extent of constitutive activation of JAK3 was found. The reduction of gamma(c) protein expression also reduced GH-induced proliferation and STAT5 nuclear translocation in B lymphoblastoid cell lines. Hence, our data demonstrate that gamma(c) plays a remarkable role in either spontaneous or GH-induced cell cycle progression depending on the amount of protein expression, suggesting a potential role as enhancing cofactor in lymphoproliferation.
- Published
- 2009
- Full Text
- View/download PDF
31. Functional interaction of common gamma-chain and growth hormone receptor signaling apparatus.
- Author
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Adriani M, Garbi C, Amodio G, Russo I, Giovannini M, Amorosi S, Matrecano E, Cosentini E, Candotti F, and Pignata C
- Subjects
- Active Transport, Cell Nucleus genetics, Cell Line, Cell Line, Transformed, Cell Membrane immunology, Cell Membrane metabolism, Cell Nucleus genetics, Cell Nucleus metabolism, Cell Proliferation, Cell Transformation, Viral genetics, Cells, Cultured, Chromosomes, Human, X genetics, Genetic Linkage, Herpesvirus 4, Human genetics, Humans, Interleukin Receptor Common gamma Subunit deficiency, Interleukin Receptor Common gamma Subunit genetics, Phosphorylation, STAT5 Transcription Factor genetics, STAT5 Transcription Factor metabolism, Severe Combined Immunodeficiency genetics, Severe Combined Immunodeficiency immunology, Tyrosine metabolism, Interleukin Receptor Common gamma Subunit physiology, Receptors, Somatotropin physiology, Severe Combined Immunodeficiency metabolism, Signal Transduction genetics, Signal Transduction immunology
- Abstract
We previously reported on an X-linked SCID (X-SCID) patient, who also had peripheral growth hormone (GH) hyporesponsiveness and abnormalities of the protein phosphorylation events following GH receptor (GHR) stimulation. In the present study, we examined a potential role of common cytokine receptor gamma-chain (gammac) in GHR signaling using EBV-transformed lymphocytes from healthy subjects and gammac-negative X-SCID patients. We demonstrated that the proliferative response to GH stimulation of the B cell lines of gammac-negative patients was impaired despite a comparable cellular expression of GHR molecules to controls. In patients, after GH stimulation, no phosphorylation of STAT5 was observed. In addition, the molecule localization through confocal microscopy revealed that in B cell lines of patients no nuclear translocation of STAT5b following GH stimulation occurred differently from controls. Biochemical analysis of the nuclear extracts of gammac-negative cell lines provided further evidence that the amount of STAT5b and its phosphorylated form did not increase following GH stimulation. In patients, cells reconstituted with wild-type gammac abnormal biochemical and functional events were restored resulting in nuclear translocation of STAT5. Confocal experiments revealed that GHR and gammac were colocalized on the cell membrane. Our study demonstrates the existence of a previously unappreciated relationship between GHR-signaling pathway and gammac, which is required for the activation of STAT5b in B cell lines. These data also confirm that growth failure in X-SCID is primarily related to the genetic alteration of the IL2RG gene.
- Published
- 2006
- Full Text
- View/download PDF
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