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RESEARCH PRODUCT
Mast cells contribute to autoimmune diabetes by releasing interleukin-6 and failing to acquire a tolerogenic IL-10+ phenotype
Marika FalconeAlessandra MandelliClaudio TripodoCarlo PucilloEster BadamiGiorgia GriVera UsuelliElena BettoCarla GuarnottaLuca DanelliSara CapollaChiara SoriniBarbara FrossiSabrina Ingraosubject
0301 basic medicineBlood GlucoseAutoimmune diabeteAutoimmunityNodmedicine.disease_causeT-Lymphocytes RegulatoryAutoimmunityImmune toleranceSettore MED/13 - EndocrinologiaMiceAutoimmune diabetes0302 clinical medicineMice Inbred NODImmunology and AllergyNOD miceMice KnockoutInterleukin-17Forkhead Transcription FactorsFlow CytometryImmunohistochemistryhumanitiesInterleukin-10Interleukin 10Tumor necrosis factor alphaImmunologySettore MED/50 - Scienze Tecniche Mediche ApplicateMice TransgenicLaser Capture MicrodissectionReal-Time Polymerase Chain Reactionbehavioral disciplines and activities03 medical and health sciencesIslets of LangerhansImmune systemChymasesmedicineAnimalsInflammationInnate immune systembusiness.industryInterleukin-6Immune toleranceSettore MED/46 - Scienze Tecniche di Medicina di LaboratorioAutoimmune diabetes; Immune tolerance; Interleukin-10; Interleukin-6; Mast cells030104 developmental biologyDiabetes Mellitus Type 1ImmunologyMast cellsTh17 CellsMast cells; Autoimmune diabetes; Interleukin-6; Immune tolerance; Interleukin-10business030215 immunologydescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-01-01 |