Myeloid Cell Hypoxia-Inducible Factors Promote Resolution of Inflammation in Experimental Colitis.
Front Immunol
; 9: 2565, 2018.
Article
en En
| MEDLINE
| ID: mdl-30455703
ABSTRACT
Colonic tissues in Inflammatory Bowel Disease (IBD) patients exhibit oxygen deprivation and activation of hypoxia-inducible factor 1α and 2α (HIF-1α and HIF-2α), which mediate cellular adaptation to hypoxic stress. Notably, macrophages and neutrophils accumulate preferentially in hypoxic regions of the inflamed colon, suggesting that myeloid cell functions in colitis are HIF-dependent. By depleting ARNT (the obligate heterodimeric binding partner for both HIFα subunits) in a murine model, we demonstrate here that myeloid HIF signaling promotes the resolution of acute colitis. Specifically, myeloid pan-HIF deficiency exacerbates infiltration of pro-inflammatory neutrophils and Ly6C+ monocytic cells into diseased tissue. Myeloid HIF ablation also hinders macrophage functional conversion to a protective, pro-resolving phenotype, and elevates gut serum amyloid A levels during the resolution phase of colitis. Therefore, myeloid cell HIF signaling is required for efficient resolution of inflammatory damage in colitis, implicating serum amyloid A in this process.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteína Amiloide A Sérica
/
Hipoxia de la Célula
/
Colitis
/
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico
/
Subunidad alfa del Factor 1 Inducible por Hipoxia
/
Macrófagos
/
Neutrófilos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2018
Tipo del documento:
Article