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

作者：Carlos Daniela; Yaochite Juliana N U; Rocha Fernanda A; Toso Vanina D; Malmegrim Kelen C R; Ramos Simone G; Jamur Maria C; Oliver Constance; Camara Niels O; Andrade Marcus V M; Cunha Fernando Q; Silva Joao S^*

来源：European Journal of Immunology, 2015, 45(10): 2873-2885.

DOI：10.1002/eji.201545498

• Mast cell
• Regulatory T cell
• Tc17 cell
• Th17 cell
• Type 1 diabetes (T1D)

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-, 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.

• 出版日期2015-10