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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Hypoxia enhances ILC3 responses through HIF-1 alpha-dependent mechanism

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Author(s):
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Fachi, J. L. [1, 2] ; Pral, L. P. [2] ; dos Santos, J. A. C. [2] ; Codo, A. C. [3] ; de Oliveira, S. [2] ; Felipe, J. S. [2] ; Zambom, F. F. F. [4] ; Camara, N. O. S. [5, 4] ; Vieira, P. M. M. M. [6, 7, 3] ; Colonna, M. [1] ; Vinolo, M. A. R. [6, 2, 7]
Total Authors: 11
Affiliation:
[1] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 - USA
[2] Univ Estadual Campinas, Inst Biol, Dept Genet Evolut Microbiol & Immunol, Lab Immunoinflammat, Campinas - Brazil
[3] Univ Estadual Campinas, Inst Biol, Dept Genet & Evolut Microbiol & Immunol, Lab Immunometabolism, Campinas - Brazil
[4] Univ Sao Paulo, Fac Med, Dept Clin Med, Renal Div, Sao Paulo - Brazil
[5] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil
[6] Expt Med Res Cluster, Campinas - Brazil
[7] Univ Estadual Campinas, Obes & Comorbol Res Ctr OCRC, Campinas - Brazil
Total Affiliations: 7
Document type: Journal article
Source: MUCOSAL IMMUNOLOGY; v. 14, n. 4 JAN 2021.
Web of Science Citations: 1
Abstract

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-1 alpha was chemically stabilized and was reversed when HIF-1 was blocked. The increased activation of ILC3 relied on a HIF-1 alpha-dependent transcriptional program, but not on mTOR-signaling or a switch to glycolysis. HIF-1 alpha 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-1 alpha activation in intestinal ILC3 is relevant for their functions in steady state and infectious conditions. (AU)

FAPESP's process: 19/11662-0 - Participation of the FFAR2 receptor in the inflammation in a DSS-induced colitis model
Grantee:Sarah de Oliveira
Support type: Scholarships in Brazil - Master
FAPESP's process: 18/02208-1 - Effect of short chain fatty acids on the function of type 3 innate lymphoid cells: involvement of the FFAR2 receptor in this process
Grantee:Laís Passariello Pral
Support type: Scholarships in Brazil - Master
FAPESP's process: 18/22505-0 - Effect of 12-oleic acid ester of hydroxy fatty acid (12-OAHSA) on inflammatory and metabolic pathways of macrophage activation
Grantee:Ana Campos Codo
Support type: Scholarships in Brazil - Master
FAPESP's process: 19/06372-3 - Multiparametric flow cytometry
Grantee:Alessandro dos Santos Farias
Support type: Multi-user Equipment Program
FAPESP's process: 17/06577-9 - Mechanisms involved in the protective effect of short-chain fatty acids against Clostridium difficile-associated colitis
Grantee:José Luís Fachi
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 18/15313-8 - Investigation of the molecular mechanisms involved in the interaction between microbiota-derived metabolites and host cells during inflammation
Grantee:Marco Aurélio Ramirez Vinolo
Support type: Research Grants - Young Investigators Grants - Phase 2
FAPESP's process: 15/15626-8 - Macrophages and T lymphocytes immunometabolism in metabolic and inflammatory diseases
Grantee:Pedro Manoel Mendes de Moraes Vieira
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 17/16280-3 - Role of the interaction between HIF-1 and the short chain fatty acids in the colon in physiological and pathologycal conditions (intestinal inflammation)
Grantee:Marco Aurélio Ramirez Vinolo
Support type: Regular Research Grants