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Interleukin‐17/interleukin‐17 receptor axis elicits intestinal neutrophil migration, restrains gut dysbiosis and lipopolysaccharide translocation in high‐fat diet‐induced metabolic syndrome model
Author(s) -
Pérez Malena M.,
Martins Larissa M. S.,
Dias Murilo S.,
Pereira Camila A.,
Leite Jefferson A.,
Gonçalves Enrico C. S.,
de Almeida Paula Z.,
de Freitas Emanuelle N.,
Tostes Rita C.,
Ramos Simone G.,
de Zoete Marcel R.,
Ryffel Bernhard,
Silva João S.,
Carlos Daniela
Publication year - 2019
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.13028
Subject(s) - akkermansia muciniphila , biology , endocrinology , medicine , cxcl1 , interleukin 22 , intestinal epithelium , lipopolysaccharide , immunology , interleukin , dysbiosis , mesenteric lymph nodes , cytokine , tlr2 , chemokine , tlr4 , gut flora , inflammation , immune system , epithelium , genetics
Summary Sound evidence supports a role for interleukin‐17 (IL‐17) ‐producing γδ 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 9 weeks. 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.