| Full text | |
| Author(s): Show less - |
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]
Total Authors: 14
|
| Affiliation: | [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
Total Affiliations: 6
|
| Document type: | Journal article |
| Source: | IMMUNOLOGY; v. 156, n. 4, p. 339-355, APR 2019. |
| Web of Science Citations: | 2 |
| Abstract | |
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) | |
| FAPESP's process: | 12/10395-0 - Role of NLRs receptors in immunoregulation mechanisms of the type 1 and 2 diabetes: identification of potential therapeutic targets |
| Grantee: | Daniela Carlos Sartori |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 13/08216-2 - CRID - Center for Research in Inflammatory Diseases |
| Grantee: | Fernando de Queiroz Cunha |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 14/21020-2 - Study of intestinal Th17 response role in obesity-induced type 2 diabetes |
| Grantee: | Malena Martínez Pérez |
| Support Opportunities: | Scholarships in Brazil - Master |