Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
Author(s):
Show less -
Carlos, Daniela [1, 2] ; Yaochite, Juliana N. U. [1, 2] ; Rocha, Fernanda A. [1, 2] ; Toso, Vanina D. [3] ; Malmegrim, Kelen C. R. [4] ; Ramos, Simone G. [5] ; Jamur, Maria C. [3] ; Oliver, Constance [3] ; Camara, Niels O. [6] ; Andrade, Marcus V. M. [7] ; Cunha, Fernando Q. [8] ; Silva, Joao S. [1, 2]
Total Authors: 12
Affiliation:
[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem, BR-14049900 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Immunol, BR-14049900 Ribeirao Preto, SP - Brazil
[3] Univ Sao Paulo, Sch Med Ribeirao Preto, Mol & Cellular Biol, BR-14049900 Ribeirao Preto, SP - Brazil
[4] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Toxicol & Bromatol Anal, BR-14049900 Ribeirao Preto, SP - Brazil
[5] Univ Sao Paulo, Sch Med Ribeirao Preto, Pathol, BR-14049900 Ribeirao Preto, SP - Brazil
[6] Univ Sao Paulo, Inst Biomed Sci ICB, Dept Immunol, Sao Paulo, SP - Brazil
[7] Univ Fed Minas Gerais, Sch Med, Dept Clin Med, Belo Horizonte, MG - Brazil
[8] Univ Sao Paulo, Sch Med Ribeirao Preto, Pharmacol, BR-14049900 Ribeirao Preto, SP - Brazil
Total Affiliations: 8
Document type: Journal article
Source: European Journal of Immunology; v. 45, n. 10, p. 2873-2885, OCT 2015.
Web of Science Citations: 10
Abstract

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. (AU)