Hypoxia-inducible factors in T lymphocyte differentiation and function. A Review in the Theme: Cellular Responses to Hypoxia.
Low oxygen concentrations or hypoxia is a trait common to inflamed tissues. Therefore it is not surprising that pathways of hypoxic stress response, largely governed by hypoxia-inducible factors (HIF), are highly relevant to the proper function of immune cells. HIF expression and stabilization in immune cells can be triggered not only by hypoxia, but also by a variety of stimuli and pathological stresses associated with leukocyte activation and inflammation. In addition to its role as a sensor of oxygen scarcity, HIF is also a major regulator of immune cell metabolic function. Rapid progress is being made in elucidating the roles played by HIF in diverse aspects of both innate and adaptive immunity. Here we discuss a number of breakthroughs that have shed light on how HIF expression and activity impact the differentiation and function of diverse T cell populations. The insights gained from these findings may serve as the foundation for future therapies aimed at fine-tuning the immune response.
Department of Rheumatology and Immunology, Anhui Provincial Hospital, Affiliated to Anhui Medical University, Hefei, China; and.
Jin-Hui
JH
Tao
Immunology and Hematopoiesis Division, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Joseph
J
Barbi
Immunology and Hematopoiesis Division, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland fpan1@jhmi.edu jbarbi1@jhmi.edu.
Fan
F
Pan
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D015687:Cell Hypoxia; D006801:Humans; D000860:Hypoxia / Q000276:immunology / Q000378:metabolism*; D051793:Hypoxia-Inducible Factor 1 / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D010100:Oxygen / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
D051793:Hypoxia-Inducible Factor 1; D010100:Oxygen
T cells; hypoxia-inducible factor; immune activation; inflammation; metabolism