Hypoxia enhances ILC3 responses through HIF-1α-dependent mechanism
| Autor: | Marco Colonna, J. A. dos Santos, P M M M Vieira, Jaqueline de Souza Felipe, S de Oliveira, Niels Olsen Saraiva Câmara, F F F Zambom, Laís Passariello Pral, José Luís Fachi, Marco Aurélio Ramirez Vinolo, Ana Campos Codo |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cellular adaptation Immunology Lymphocyte Activation Article 03 medical and health sciences Mice INFECÇÕES BACTERIANAS GRAM-POSITIVAS 0302 clinical medicine In vivo medicine Immunology and Allergy Compartment (development) Animals Glycolysis Hypoxia Mice Knockout Chemistry Protein Stability TOR Serine-Threonine Kinases Innate lymphoid cell Correction Hypoxia (medical) Nuclear Receptor Subfamily 1 Group F Member 3 Hypoxia-Inducible Factor 1 alpha Subunit Intestinal epithelium Immunity Innate Lymphocyte Subsets Cell biology Mitochondria Disease Models Animal 030104 developmental biology 030220 oncology & carcinogenesis Clostridium Infections Disease Susceptibility medicine.symptom Homeostasis Signal Transduction |
| Zdroj: | Mucosal Immunology Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1935-3456 1933-0219 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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