title: Mast cells control insulitis and increase Treg cells to confer protection against STZ-induced type 1 diabetes in mice.
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-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.
authors.affiliation: Departments of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Daniela
authors.initials: D
authors.lastname: Carlos
authors.affiliation: Departments of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Juliana N U
authors.initials: JN
authors.lastname: Yaochite
authors.affiliation: Departments of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Fernanda A
authors.initials: FA
authors.lastname: Rocha
authors.affiliation: Molecular and Cellular Biology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Vanina D
authors.initials: VD
authors.lastname: Toso
authors.affiliation: Department of Clinical, Toxicological and Bromatological Analysis, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Kelen C R
authors.initials: KC
authors.lastname: Malmegrim
authors.affiliation: Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Simone G
authors.initials: SG
authors.lastname: Ramos
authors.affiliation: Molecular and Cellular Biology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Jamur
authors.affiliation: Molecular and Cellular Biology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Constance
authors.initials: C
authors.lastname: Oliver
authors.affiliation: Department of Immunology, Institute of Biomedical Science (ICB), University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Niels O
authors.initials: NO
authors.lastname: Camara
authors.affiliation: Department of Medical Clinical, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Marcus V M
authors.initials: MV
authors.lastname: Andrade
authors.affiliation: Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.affiliation: Departments of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: João S
authors.initials: JS
authors.lastname: Silva
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D016207:Cytokines
keywords: Mast cell; Regulatory T cell; Tc17 cell; Th17 cell; Type 1 diabetes (T1D)