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Hypoxia enhances ILC3 responses through HIF-1α-dependent mechanism.
Fachi, J L; Pral, L P; Dos Santos, J A C; Codo, A C; de Oliveira, S; Felipe, J S; Zambom, F F F; Câmara, N O S; Vieira, P M M M; Colonna, M; Vinolo, M A R.
Afiliação
  • Fachi JL; Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
  • Pral LP; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA.
  • Dos Santos JAC; Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
  • Codo AC; Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
  • de Oliveira S; Laboratory of Immunometabolism, Department of Genetics and Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
  • Felipe JS; Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
  • Zambom FFF; Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
  • Câmara NOS; Renal Division, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
  • Vieira PMMM; Renal Division, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
  • Colonna M; Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
  • Vinolo MAR; Laboratory of Immunometabolism, Department of Genetics and Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
Mucosal Immunol ; 14(4): 828-841, 2021 07.
Article em En | MEDLINE | ID: mdl-33446906
Group 3 innate lymphoid cells (ILC3) have a prominent role in the maintenance of intestine mucosa homeostasis. The hypoxia-inducible factor (HIF) is an important modulator of immune cell activation and a key mechanism for cellular adaptation to oxygen deprivation. However, its role on ILC3 is not well known. In this study, we investigated how a hypoxic environment modulates ILC3 response and the subsequent participation of HIF-1 signaling in this process. We found increased proliferation and activation of intestinal ILC3 at low oxygen levels, a response that was phenocopied when HIF-1α was chemically stabilized and was reversed when HIF-1 was blocked. The increased activation of ILC3 relied on a HIF-1α-dependent transcriptional program, but not on mTOR-signaling or a switch to glycolysis. HIF-1α deficiency in RORyt compartment resulted in impaired IL-17 and IL-22 production by ILC3 in vivo, which reflected in a lower expression of their target genes in the intestinal epithelium and an increased susceptibility to Clostridiodes difficile infection. Taken together, our results show that HIF-1α activation in intestinal ILC3 is relevant for their functions in steady state and infectious conditions.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Subpopulações de Linfócitos / Subunidade alfa do Fator 1 Induzível por Hipóxia / Imunidade Inata / Hipóxia Tipo de estudo: Etiology_studies / Prognostic_studies Limite: Animals Idioma: En Revista: Mucosal Immunol Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
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XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Subpopulações de Linfócitos / Subunidade alfa do Fator 1 Induzível por Hipóxia / Imunidade Inata / Hipóxia Tipo de estudo: Etiology_studies / Prognostic_studies Limite: Animals Idioma: En Revista: Mucosal Immunol Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos