Mast cells control insulitis and increase Treg cells to confer protection against STZ-induced type 1 diabetes in mice

Autor: Daniela, Carlos, Juliana N U, Yaochite, Fernanda A, Rocha, Vanina D, Toso, Kelen C R, Malmegrim, Simone G, Ramos, Maria C, Jamur, Constance, Oliver, Niels O, Camara, Marcus V M, Andrade, Fernando Q, Cunha, João S, Silva
Rok vydání: 2015
Předmět:
Zdroj: European journal of immunology. 45(10)
ISSN: 1521-4141
Popis: Quantitative alterations in mast cell numbers in pancreatic lymph nodes (PLNs) have been reported to be associated with type 1 diabetes (T1D) progression, but their potential role during T1D remains unclear. In this study, we evaluated the role of mast cells in T1D induced by multiple low-dose streptozotocin (MLD-STZ) treatments, using two strains of mast cell-deficient mice (W/W(v) or Wsh/Wsh) and the adoptive transfer of mast cells. Mast cell deficient mice developed severe insulitis and accelerated hyperglycemia, with 100% of mice becoming diabetic compared to their littermates. In parallel, these diabetic mice had decreased numbers of T regulatory (Treg) cells in the PLNs. Additionally, mast cell deficiency caused a significant reduction in IL-10, TGF-β, and IL-6 expression in the pancreatic tissue. Interestingly, IL-6-deficient mice are more susceptible to T1D associated with reduced Treg-cell numbers in the PLNs, but mast cell transfer from wild-type mice induced protection to T1D in these mice. Finally, mast cell adoptive transfer prior to MLD-STZ administration conferred resistance to T1D, promoted increased Treg cells, and decreased IL-17-producing T cells in the PLNs. Taken together, our results indicate that mast cells are implicated in resistance to STZ-induced T1D via an immunological tolerance mechanism mediated by Treg cells.
Databáze: OpenAIRE