Hypoxia-inducible factor 1: A link between metabolism and T cell differentiation and a potential therapeutic target

Naïve T cells activated by antigen-presenting cells (APC) can be differentiated into at least four major types of T-helper (T(H)) cells: T(H)1, T(H)2, T(H)17 and inducible regulatory T cells (iTreg) based on their unique cytokine production profiles and characteristic functions.(1) T(H)1 produce interferon-γ (IFNγ) and are important for protective immune responses to intracellular viral, bacterial and parasitic infection. T(H)2 cells produce interleukin-4 (IL-4), IL-5, IL-23 and are critical for controlling extracellular parasites such as helminthes. T(H)17 cells are responsible for expelling extracellular bacteria and fungi through secretion of IL-17a, IL-17f and IL-22.(2) These cells however are perhaps better known for their propensity to drive autoimmune responses. Tregs including naturally occurring regulatory T cells (nTreg) play important roles in the suppressive control of both innate and adaptive immunity in vivo.(3)(,)(4)