Differentiation of follicular helper T cells by salivary gland epithelial cells in primary Sjögren's syndrome |
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| Institution: | 1. Immunorhumatologie moléculaire, INSERM UMR S_1109, Centre de Recherche en Immunologie et Hématologie, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg, France;2. Service de Rhumatologie, Centre National de Référence pour les Maladies Systémiques Autoimmunes Rares, Hôpitaux Universitaires de Strasbourg, Strasbourg, France;3. University of California San Francisco, Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, 374 Parnassus Avenue, San Francisco, CA 94143, USA;4. Corinne Miceli-Richard, Xavier Mariette: Université Paris-Sud 11, Rhumatologie, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris (AP-HP), Le Kremlin Bicêtre, France;1. Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK;2. Division of Molecular and Clinical Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK;1. Programa de Biología Celular y Molecular, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile;2. Departamento de Reumatología, Clínica INDISA, Santiago, Chile;3. Center for Molecular Studies of the Cell (CEMC), Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santiago, Chile;4. Escuela Dental, Facultad de Ciencias, Universidad Mayor, Santiago, Chile;5. Programa de Inmunología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile;1. Division of Rheumatology, Department of Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China;2. Division of Nephrology, Department of Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China;3. Division of Nephrology, Department of Medicine, Shenzhen Baoan Shiyan People’s Hospital, Shenzhen, Guangdong 518005, China;4. Department of Pathology, Brigham and Women''s Hospital, Harvard Medical School, Boston, MA, USA;1. Dept. of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands;2. Dept. of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands;3. Dept. of Oral and Maxillofacial Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands |
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| Abstract: | Follicular helper T cells (Tfh), which play a pivotal role in B cell activation and differentiation in lymphoid structures, secrete IL-21 whose augmented secretion is a hallmark of several autoimmune diseases. To decipher the cellular and molecular interactions occurring in salivary glands of patients suffering from primary Sjögren's syndrome (pSS), we investigated whether salivary gland epithelial cells (SGECs) were capable to induce Tfh differentiation. Co-cultures of naïve CD4+ T cells and SGECs from both patients with pSS and controls were performed. Here, we report that IL-6 and ICOSL expression by SGECs contributes to naïve CD4+ T differentiation into Tfh cells, as evidenced by their acquisition of a specific phenotype, characterized by Bcl-6, ICOS and CXCR5 expression and IL-21 secretion, but also but by their main functional feature: the capacity to enhance B lymphocytes survival. We demonstrated an increase of serum IL-21 with systemic activity. Finally, we analyzed the potential occurrence of a genetic association between IL-21 or IL-21R gene polymorphisms and pSS or elevated IL-21 secretion. This study, which demonstrates a direct induction of Tfh differentiation by SGECs, emphasizes a yet unknown pathogenic role of SGECs and suggests that Tfh and IL-21 might be relevant biomarkers and/or therapeutic targets in primary Sjögren's syndrome. |
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| Keywords: | Sjögren's syndrome Epithelial cells Germinal centers Follicular helper T cells IL-21 |
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