Increased HIF-1 alpha expression in T cells and associated with enhanced Th17 pathway in systemic lupus erythematosus

Background/Purpose: Recent emerging evidence indicates that dysfunction of metabolic remodeling underlies aberrant T cell immune responses in systemic lupus erythematosus (SLE). This study was undertaken to investigate the expression of HIF-1a, a regulator of metabolic reprogramming, in T cells from SLE. Methods: HIF-1a expression in T lymphocytes from SLE patients was examined by quantitative polymerase chain reaction (PCR) and the protein expression was analyzed with intracellular staining in flow cytometry. HIF-1a was overexpressed in murine CD4 T cells via transducing T cells with HIF-1a containing lentivirus. The expression of HIF- 1a, metabolic- and Th17associated genes in T cells from SLE patients and its association with clinical manifestation was analyzed. Results: HIF-1a expression is increased in CD4 T cells from SLE patients both in intracellular staining and quantitative PCR analysis. In addition, there is enhanced HIF- 1a expression in Th17-skewing murine T cells, and lentivirus-mediated HIF-1a overexpression promotes Th17 differentiation. Moreover, HIF-1a gene expression is positively correlated with the expression of glycolysis- and IL-17-associated genes in SLE patients. Conclusion: HIF-1a expression is increased in T cells from SLE patients, and is positively correlated with glycolysis- and Th17- associated pathway, implicating HIF-1a contributes to the activation of Th17 cells in SLE, and represents a potential novel therapeutic target. Copyright (c) 2022, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).