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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
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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]
Número total de Autores: 12
Afiliação do(s) autor(es):
[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
Número total de Afiliações: 8
Tipo de documento: Artigo Científico
Fonte: European Journal of Immunology; v. 45, n. 10, p. 2873-2885, OCT 2015.
Citações Web of Science: 10
Resumo

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)

Processo FAPESP: 08/50598-1 - Papel dos mastócitos na diabetes experimental e no aumento de suscetibilidade ao desenvolvimento da sepse
Beneficiário:Daniela Carlos Sartori
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado