title: Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function.
abstract: Oxygen is a molecule that is central to cellular respiration and viability, yet there are multiple physiologic and pathological contexts in which cells experience conditions of insufficient oxygen availability, a state known as hypoxia. Given the metabolic challenges of a low oxygen environment, hypoxia elicits a range of adaptive responses at the cellular, tissue, and systemic level to promote continued survival and function. Within this context, T lymphocytes are a highly migratory cell type of the adaptive immune system that frequently encounters a wide range of oxygen tensions in both health and disease. It is now clear that oxygen availability regulates T cell differentiation and function, a response orchestrated in large part by the hypoxia-inducible factor transcription factors. Here, we discuss the physiologic scope of hypoxia and hypoxic signaling, the contribution of these pathways in regulating T cell biology, and current gaps in our understanding. Finally, we discuss how emerging therapies that modulate the hypoxic response may offer new modalities to alter T cell function and the outcome of acute and chronic pathologies.
authors.affiliation: Mucosal Inflammation Program, Department of Anesthesiology, School of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Eóin N
authors.initials: EN
authors.lastname: McNamee
authors.forename: Darlynn
authors.initials: D
authors.lastname: Korns Johnson
authors.forename: Dirk
authors.initials: D
authors.lastname: Homann
authors.forename: Eric T
authors.initials: ET
authors.lastname: Clambey
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000276:immunology*; D002454:Cell Differentiation; D006801:Humans; D000860:Hypoxia / Q000276:immunology*; D010100:Oxygen / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D010100:Oxygen