Interleukin-23 promotes intestinal T helper type17 immunity and ameliorates obesity-associated metabolic syndrome in a murine high-fat diet model

Autor(es):Mostrar menos -

Martins, Larissa M. S. ^{[1, 2]} ; Perez, Malena M. ^{[1, 2]} ; Pereira, Camila A. ^[3] ; Costa, Frederico R. C. ^{[1, 2]} ; Dias, Murilo S. ^{[1, 2]} ; Tostes, Rita C. ^[3] ; Ramos, Simone G. ^[4] ; de Zoete, Marcel R. ^[5] ; Ryffel, Bernhard ^{[6, 7, 8]} ; Silva, Joao S. ^{[1, 2]} ; Carlos, Daniela ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Immunol, Ribeirao Preto, SP - Brazil

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

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pathol & Legal Med, Ribeirao Preto, SP - Brazil

^[5] Univ Utrecht, Dept Infect Dis & Immunol, Utrecht - Netherlands

^[6] Univ Orleans, Mol Immunol, Orleans - France

^[7] CNRS, UMR6218, INEM, Orleans - France

^[8] Univ Cape Town, Inst Infect Dis & Mol Med, IDM, Cape Town - South Africa

• Tipo de documento: Artigo Científico
• Fonte: IMMUNOLOGY; v. 154, n. 4, p. 624-636, AUG 2018.
• Citações Web of Science: 4

Resumo

We addressed the role of interleukin-23 (IL-23) in driving the intestinal T helper type 17 (Th17) response during obesity and metabolic syndrome progression induced by a high-fat diet (HFD). Diet-induced obese and lean mice received HFD or control diet (CTD), respectively, for 20 weeks. The nutritional, metabolic and immune parameters were examined at weeks 9 and 20. Gene and protein IL-23p19 and IL-23 receptor expression was increased in the ileum of obese wild-type mice (WT) fed the HFD for 9 weeks. Mice lacking IL-23 and fed the HFD exhibited greater weight gain, higher fat accumulation, adipocyte hypertrophy and hepatic steatosis. Notably, these mice had more glucose intolerance, insulin resistance and associated metabolic alterations, such as hyperinsulinaemia and hyperlipidaemia. IL-23 deficiency also significantly reduced protein levels of IL-17, CCL20 and neutrophil elastase in the ileum and reduced Th17 cell expansion in the mesenteric lymph nodes of the HFD mice. Of importance, IL-23-deficient mice exhibited increased gut permeability and blood bacterial translocation compared with WT mice fed HFD. Finally, metagenomics analysis of gut microbiota revealed a dramatic outgrowth of Bacteroidetes over Firmicutes phylum with the prevalence of Bacteroides genera in the faeces of IL-23-deficient mice after HFD. In summary, IL-23 appears to maintain the Th17 response and neutrophil migration into the intestinal mucosa, minimizing the gut dysbiosis and protecting against obesity and metabolic disease development in mice. (AU)

• Processo FAPESP: 14/15462-2 - Avaliação do papel do receptor NOD2 na resistência à insulina e diabetes do tipo 2
• Beneficiário: Larissa Marfori Sampaio Martins
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica