Mast cells contribute to autoimmune diabetes by releasing interleukin-6 and failing to acquire a tolerogenic IL-10(+) phenotype

Carla Guarnotta, Claudio Tripodo, Sabrina Ingrao, Vera Usuelli, Elena Betto, Chiara Sorini, Luca Danelli, Sara Capolla, Alessandra Mandelli, Marika Falcone, Ester Badami, Barbara Frossi, Giorgia Gri, Carlo Pucillo

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)29-38
Number of pages10
JournalClinical Immunology
Volume178
Publication statusPublished - 2017

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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