Tolerogenic effect of mesenchymal stromal cells on gliadin-specific T lymphocytes in celiac disease |
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| Institution: | 1. Clinica Medica I, Fondazione IRCCS Policlinico San Matteo, Università di Pavia, Pavia, Italy;2. Istituto Scienze dell''Alimentazione, CNR Avellino, Italy;3. Dipartimento di Bioscienze, Università di Parma, Italy (currently affiliated with Dipartimento di Biochimica e Biologia Molecolare, Università di Parma, Italy; Dipartimento di Medicina Occupazionale, Ergonomia e Disabilità, Laboratorio di Nanotecnologia, Fondazione IRCCS Salvatore Maugeri, Università di Pavia, Italy);4. Laboratorio di Nanotecnologia, Fondazione IRCCS Salvatore Maugeri, Università di Pavia, Italy (currently affiliated with Dipartimento di Medicina Occupazionale, Ergonomia e Disabilità, Laboratorio di Nanotecnologia, Fondazione IRCCS Salvatore Maugeri, Università di Pavia, Italy; Dipartimento di Medicina Molecolare, Centro di Ingegneria Tissutale, INSTM UdR Pavia, Università di Pavia, Italy);5. Servizio di Endoscopia Digestiva, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy;6. Servizio di Immunogenetica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy;7. Dipartimento di Onco-Ematologia Pediatrica e Medicina Trasfusionale, Ospedale Bambino Gesù, Roma e Università degli Studi di Pavia, Pavia, Italy;8. Servizio di Biometria e Statistica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy;1. Centre de Recherche du CHU Ste-Justine, Université de Montréal, Montréal, Québec, Canada;2. Département de Pharmacologie, Université de Montréal, Montréal, Québec, Canada;3. Département de Somatologie, Université de Montréal, Montréal, Québec, Canada;1. Centre for Immune Regulation and Department of Immunology, Oslo University Hospital-Rikshospitalet, Oslo, Norway;2. Department of Pathology, Oslo University Hospital-Rikshospitalet, Oslo, Norway;3. PreventCD Project Group;4. Department of Paediatrics and Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary;5. Heim Pal Children''s Hospital, Budapest, Hungary;6. Paediatric Gastroenterology Unit, Hospital Universitari Sant Joan de Reus, Universitat Rovira i Virgili, Tarragona, Spain;7. Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway;8. Institute of Clinical Medicine, University of Oslo, Oslo, Norway;9. Centre for Immune Regulation and Department of Immunology, University of Oslo, Oslo, Norway;10. KG Jebsen Coeliac Disease Research Centre, University of Oslo, Oslo, Norway;1. Centre hospitalo-universitaire, Constantine, Algérie;2. Centre hospitalo universitaire hospices civiles strasbourg, Strasbourg, France;1. General Medical Center of the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China;2. Department of Hematopoietic Stem Cell Transplantation, Hospital Affiliated with the Academy of Military Medical Sciences, Beijing, China;1. Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People''s Hospital, Shanghai, China;2. Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Ninth People''s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China |
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| Abstract: | Background aimsCeliac disease is caused by a dysregulated immune response toward dietary gluten, whose only treatment is a lifelong gluten-free diet. We investigated the effects of mesenchymal stromal cells (MSCs) on gliadin-specific T cells, which are known to induce intestinal lesions, in view of a possible use as new therapy.MethodsBone marrow–derived MSCs and gliadin-specific T-cell lines were obtained from allogeneic donors and mucosal specimens of celiac patients, respectively. The immunosuppressant effect of MSCs was evaluated in terms of proliferative response and interferon (IFN)-γ production upon gliadin stimulation of long-term T-cell lines; the immunomodulant effect was assessed in terms of apoptotic rate, immunophenotype and cytokine profile of short-term T-cell lines generated in the presence of MSCs. Different MSC:T-cell ratios were applied, and statistics were performed as appropriate.ResultsMSCs inhibited both proliferative response and IFN-γ production of long-term T-cell lines in a dose-dependent manner while limiting the expansion of short-term T-cell lines by increasing the apoptotic rate. Moreover, a reduction of the CD4+ population and expansion of the regulatory FoxP3+ subset were found in T-cell lines cultured with MSCs, in which a significant decrease of interleukin (IL)-21, IFN-γ and IL-10 paralleled by an upregulation of transforming growth factor-β1, IL-6 and IL-8 were observed. Finally, an increase of the indoleamine 2,3-dioxygenase activity was found, possibly playing a key role in mediating these effects.ConclusionsMSCs exert potent immunomodulant effects on gliadin-specific T cells, which may be exploited for future therapeutic application in celiac disease. |
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| Keywords: | celiac disease immune tolerance mesenchymal stromal cells T lymphocytes |
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