Mast cells control insulitis and increase Treg cells to confer protection against STZ-induced type 1 diabetes in mice.
Eur J Immunol
; 45(10): 2873-85, 2015 Oct.
Article
en En
| MEDLINE
| ID: mdl-26234742
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-ß, 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.
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1
Bases de datos:
MEDLINE
Asunto principal:
Regulación de la Expresión Génica
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Linfocitos T Reguladores
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Diabetes Mellitus Experimental
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Diabetes Mellitus Tipo 1
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Mastocitos
Límite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Año:
2015
Tipo del documento:
Article
País de afiliación:
Brasil