| Full text | |
| Author(s): Show less - |
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: | 15/15626-8 - Macrophages and T lymphocytes immunometabolism in metabolic and inflammatory diseases. |
| Grantee: | Pedro Manoel Mendes de Moraes Vieira |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| 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 Opportunities: | 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 Opportunities: | Scholarships in Brazil - Master |
| 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 Opportunities: | Research Grants - Young Investigators Grants - Phase 2 |
| 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 Opportunities: | Scholarships in Brazil - Master |
| 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 Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 19/06372-3 - multiparametric flow cytometry |
| Grantee: | Alessandro dos Santos Farias |
| Support Opportunities: | Multi-user Equipment Program |
| 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 Opportunities: | Regular Research Grants |