Mast cells contribute to autoimmune diabetes by releasing interleukin-6 and failing to acquire a tolerogenic IL-10+ phenotype
| Autor: | Marika Falcone, Alessandra Mandelli, Claudio Tripodo, Carlo Pucillo, Ester Badami, Giorgia Gri, Vera Usuelli, Elena Betto, Carla Guarnotta, Luca Danelli, Sara Capolla, Chiara Sorini, Barbara Frossi, Sabrina Ingrao |
|---|---|
| Přispěvatelé: | Betto, E., Usuelli, V., Mandelli, A., Badami, E., Sorini, C., Capolla, S., Danelli, L., Frossi, B., Guarnotta, C., Ingrao, S., Tripodo, C., Pucillo, C., Gri, G., Falcone, M., Betto, Elena, Usuelli, Vera, Mandelli, Alessandra, Badami, Ester, Sorini, Chiara, Capolla, Sara, DANELLI, Luca, FROSSI, Barbara, Guarnotta, Carla, Ingrao, Sabrina, Tripodo, Claudio, PUCILLO, Carlo Ennio Michele, GRI, Giorgia, Falcone, Marika |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Blood Glucose Autoimmune diabete Autoimmunity Nod medicine.disease_cause T-Lymphocytes Regulatory Immune tolerance Settore MED/13 - Endocrinologia Mice Autoimmune diabetes 0302 clinical medicine Mice Inbred NOD Immunology and Allergy NOD mice Mice Knockout Interleukin-17 Forkhead Transcription Factors Flow Cytometry Immunohistochemistry humanities Interleukin-10 Interleukin 10 Tumor necrosis factor alpha Immunology Settore MED/50 - Scienze Tecniche Mediche Applicate Mice Transgenic Laser Capture Microdissection Real-Time Polymerase Chain Reaction behavioral disciplines and activities 03 medical and health sciences Islets of Langerhans Immune system Chymases medicine Animals Inflammation Innate immune system business.industry Interleukin-6 Settore MED/46 - Scienze Tecniche di Medicina di Laboratorio Mast cells 030104 developmental biology Diabetes Mellitus Type 1 Th17 Cells business 030215 immunology |
| Popis: | Mast cells (MCs) are innate immune cells that exert positive and negative immune modulatory functions capable to enhance or limit the intensity and/or duration of adaptive immune responses. Although MCs are crucial to regulate T cell immunity, their action in the pathogenesis of autoimmune diseases is still debated. Here we demonstrate that MCs play a crucial role in T1D pathogenesis so that their selective depletion in conditional MC knockout NOD mice protects them from the disease. MCs of diabetic NOD mice are overly inflammatory and secrete large amounts of IL-6 that favors differentiation of IL-17-secreting T cells at the site of autoimmunity. Moreover, while MCs of control mice acquire an IL-10 + phenotype upon interaction with FoxP3 + Treg cells, MCs of NOD mice do not undergo this tolerogenic differentiation. Our data indicate that overly inflammatory MCs unable to acquire a tolerogenic IL-10 + phenotype contribute to the pathogenesis of autoimmune T1D. © 2016 Elsevier Inc. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|