https://scholars.lib.ntu.edu.tw/handle/123456789/627795
標題: | Kidney tissue hypoxia dictates T cell-mediated injury in murine lupus nephritis | 作者: | PING-MIN CHEN Wilson, Parker C Shyer, Justin A Veselits, Margaret Steach, Holly R Cui, Can Moeckel, Gilbert Clark, Marcus R Craft, Joe |
關鍵字: | SET ENRICHMENT ANALYSIS; GERMINAL CENTER HYPOXIA; REDUCTIVE CARBOXYLATION; GLUTAMINE-METABOLISM; EXPRESSION; SURVIVAL; ACTIVATION; GLYCOLYSIS; BALANCE; OXYGEN | 公開日期: | 8-四月-2020 | 出版社: | AMER ASSOC ADVANCEMENT SCIENCE | 卷: | 12 | 期: | 538 | 來源出版物: | Science translational medicine | 摘要: | The kidney is a frequent target of autoimmune injury, including in systemic lupus erythematosus; however, how immune cells adapt to kidney's unique environment and contribute to tissue damage is unknown. We found that renal tissue, which normally has low oxygen tension, becomes more hypoxic in lupus nephritis. In the injured mouse tissue, renal-infiltrating CD4+ and CD8+ T cells express hypoxia-inducible factor-1 (HIF-1), which alters their cellular metabolism and prevents their apoptosis in hypoxia. HIF-1-dependent gene-regulated pathways were also up-regulated in renal-infiltrating T cells in human lupus nephritis. Perturbation of these environmental adaptations by selective HIF-1 blockade inhibited infiltrating T cells and reversed tissue hypoxia and injury in murine models of lupus. The results suggest that targeting HIF-1 might be effective for treating renal injury in autoimmune diseases. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/627795 | ISSN: | 1946-6234 | DOI: | 10.1126/scitranslmed.aay1620 |
顯示於: | 生物化學暨分子生物學科研究所 |
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