Interleukin-17/interleukin-17 receptor axis elicits intestinal neutrophil migration, restrains gut dysbiosis and lipopolysaccharide translocation in high-fat diet-induced metabolic syndrome model

Autor(es):Mostrar menos -

Perez, Malena M. ^[1] ; Martins, Larissa M. S. ^[1] ; Dias, Murilo S. ^[1] ; Pereira, Camila A. ^[2] ; Leite, Jefferson A. ^[1] ; Goncalves, Enrico C. S. ^[1] ; de Almeida, Paula Z. ^[1] ; de Freitas, Emanuelle N. ^[1] ; Tostes, Rita C. ^[2] ; Ramos, Simone G. ^[3] ; de Zoete, Marcel R. ^[4] ; Ryffel, Bernhard ^{[5, 6]} ; Silva, Joao S. ^[1] ; Carlos, Daniela ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pathol & Legal Med, Ribeirao Preto - Brazil

^[4] Univ Utrecht, Dept Infect Dis & Immunol, Utrecht - Netherlands

^[5] Univ Cape Town, Inst Infect Dis & Mol Med, IDM, Cape Town - South Africa

^[6] Univ Orleans, INEM, CNRS, Mol Immunol, UMR6218, Orleans - France

• Tipo de documento: Artigo Científico
• Fonte: IMMUNOLOGY; v. 156, n. 4, p. 339-355, APR 2019.
• Citações Web of Science: 2

Resumo

Sound evidence supports a role for interleukin-17 (IL-17) -producing T cells and IL-17-producing helper T (Th17) cells in intestinal homeostasis, especially in intestinal barrier integrity. In the present study, we aimed to evaluate the role of IL-17 cytokine in the regulation of intestinal immunity and obesity-induced metabolic syndrome (MetS) in an experimental murine model. C57BL/6 wild-type (WT) mice and mice lacking the IL-17 cytokine receptor (IL-17RA(-/-)) were fed either a control diet (CD) or a high-fat diet (HFD) for 9weeks. Our data demonstrate that IL-17RA(-/-) mice are protected against obesity, but develop hyperglycemia, hyperinsulinemia and insulin resistance. In parallel, HFD-fed IL-17RA(-/-) mice display intense inflammation in the ileum compared with WT mice on the HFD. IL-17RA(-/-) mice fed the HFD exhibit impaired neutrophil migration to the intestinal mucosa and reduced gene expression of the CXCL-1 chemokine and CXCR-2 receptor in the ileum. Interestingly, the populations of neutrophils (CD11b(+)Ly6G(+)) and anti-inflammatory macrophages (CD11b(+)CX3CR1(+)) are increased in the mesenteric lymph nodes of these mice. IL-17RA(-/-) mice on the HFD also display increased commensal bacterial translocation into the bloodstream and elevated lipopolysaccharide (LPS) levels in the visceral adipose tissue (VAT). Metagenomic analysis of bacterial 16S gene revealed increased Proteobacteria and Bacteroidetes phyla, the main representatives of Gram-negative bacteria, and reduced Akkermansia muciniphila in the fecal samples of IL-17RA(-/-) mice fed the HFD. Together, these data indicate that the IL-17/IL-17R axis drives intestinal neutrophil migration, limits gut dysbiosis and attenuates LPS translocation to VAT, resulting in protection to MetS. (AU)

• Processo FAPESP: 12/10395-0 - Papel dos receptores NLRs nos mecanismos de imunoregulação do diabetes do tipo 1 e 2: identificação de novos alvos terapêuticos
• Beneficiário: Daniela Carlos Sartori
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 14/21020-2 - Estudo do papel da resposta Th17 intestinal no diabetes tipo 2 induzido por obesidade
• Beneficiário: Malena Martínez Pérez
• Modalidade de apoio: Bolsas no Brasil - Mestrado