Kidney tissue hypoxia dictates T cell-mediated injury in murine lupus nephritis. 2020

Ping-Min Chen, and Parker C Wilson, and Justin A Shyer, and Margaret Veselits, and Holly R Steach, and Can Cui, and Gilbert Moeckel, and Marcus R Clark, and Joe Craft
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.

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.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008180 Lupus Erythematosus, Systemic A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. Libman-Sacks Disease,Lupus Erythematosus Disseminatus,Systemic Lupus Erythematosus,Disease, Libman-Sacks,Libman Sacks Disease
D008181 Lupus Nephritis Glomerulonephritis associated with autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Lupus nephritis is histologically classified into 6 classes: class I - normal glomeruli, class II - pure mesangial alterations, class III - focal segmental glomerulonephritis, class IV - diffuse glomerulonephritis, class V - diffuse membranous glomerulonephritis, and class VI - advanced sclerosing glomerulonephritis (The World Health Organization classification 1982). Glomerulonephritis, Lupus,Lupus Glomerulonephritis,Nephritis, Lupus,Glomerulonephritides, Lupus,Lupus Glomerulonephritides,Lupus Nephritides,Nephritides, Lupus
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000860 Hypoxia Sub-optimal OXYGEN levels in the ambient air of living organisms. Anoxia,Oxygen Deficiency,Anoxemia,Deficiency, Oxygen,Hypoxemia,Deficiencies, Oxygen,Oxygen Deficiencies
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018414 CD8-Positive T-Lymphocytes A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes. Suppressor T-Lymphocytes, CD8-Positive,T8 Cells,T8 Lymphocytes,CD8-Positive Lymphocytes,Suppressor T-Cells, CD8-Positive,CD8 Positive Lymphocytes,CD8 Positive T Lymphocytes,CD8-Positive Lymphocyte,CD8-Positive Suppressor T-Cell,CD8-Positive Suppressor T-Cells,CD8-Positive Suppressor T-Lymphocyte,CD8-Positive Suppressor T-Lymphocytes,CD8-Positive T-Lymphocyte,Cell, T8,Cells, T8,Lymphocyte, CD8-Positive,Lymphocyte, T8,Lymphocytes, CD8-Positive,Lymphocytes, T8,Suppressor T Cells, CD8 Positive,Suppressor T Lymphocytes, CD8 Positive,Suppressor T-Cell, CD8-Positive,Suppressor T-Lymphocyte, CD8-Positive,T-Cell, CD8-Positive Suppressor,T-Cells, CD8-Positive Suppressor,T-Lymphocyte, CD8-Positive,T-Lymphocyte, CD8-Positive Suppressor,T-Lymphocytes, CD8-Positive,T-Lymphocytes, CD8-Positive Suppressor,T8 Cell,T8 Lymphocyte

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