Loss of hypoxia inducible factor-1α aggravates γδ T-cell-mediated inflammation during acetaminophen-induced liver injury

Hepatology Communications
Tomohiro SuzukiNobuhito Goda

Abstract

Acetaminophen (APAP)-induced liver injury is closely associated with acute hepatic inflammation. Hypoxia-inducible factor-1 (HIF-1) is activated during immunological processes and regulates gene expressions in various types of immune cells. Although HIF-1 controls the differentiation and functions of conventional T cells in chronic inflammation, the pathological importance of HIF-1 in innate-like T cells during acute inflammation remains unknown. Here, we investigated the role of HIF-1 in innate-like γδ T cells during APAP-induced acute liver injury. In response to APAP administration, T-cell-specific Hif-1α gene knockout mice sustained severe liver damage compared to wild-type control mice but without any impacts on the initial hepatic insult. This severe liver damage was accompanied by excessive neutrophil infiltration into the liver, increased serum interleukin (IL)-17A levels, and increased hepatic expressions of C-X-C chemokine ligand (Cxcl) 1 and Cxcl2. Neutrophil depletion and IL-17A neutralization completely abolished the aggravated phenotypes in T-cell-specific Hif-1α gene knockout mice. Loss of the Hif-1α gene enhanced the aberrant accumulation of IL-17A-producing innate-like γδ T cells in the affected liver with no a...Continue Reading

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Citations

Jun 22, 2019·Experimental & Molecular Medicine·Jae W LeeHolger K Eltzschig
Dec 10, 2019·American Journal of Physiology. Renal Physiology·Sang Jun HanH Thomas Lee
Aug 9, 2020·International Journal of Molecular Sciences·Chiara Corrado, Simona Fontana

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BETA
flow cytometry
PMA

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