HIF transcription factors, inflammation, and immunity

Immunity. 2014 Oct 16;41(4):518-28. doi: 10.1016/j.immuni.2014.09.008.


The hypoxic response in cells and tissues is mediated by the family of hypoxia-inducible factor (HIF) transcription factors; these play an integral role in the metabolic changes that drive cellular adaptation to low oxygen availability. HIF expression and stabilization in immune cells can be triggered by hypoxia, but also by other factors associated with pathological stress: e.g., inflammation, infectious microorganisms, and cancer. HIF induces a number of aspects of host immune function, from boosting phagocyte microbicidal capacity to driving T cell differentiation and cytotoxic activity. Cellular metabolism is emerging as a key regulator of immunity, and it constitutes another layer of fine-tuned immune control by HIF that can dictate myeloid cell and lymphocyte development, fate, and function. Here we discuss how oxygen sensing in the immune microenvironment shapes immunological response and examine how HIF and the hypoxia pathway control innate and adaptive immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptation, Physiological
  • Adaptive Immunity*
  • Animals
  • Bacterial Infections / immunology
  • Basic Helix-Loop-Helix Transcription Factors / immunology*
  • Cell Differentiation / immunology
  • Cell Hypoxia / immunology
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / immunology*
  • Immunity, Innate*
  • Inflammation / genetics
  • Inflammation / immunology*
  • Mice
  • Neoplasms / immunology
  • Oxygen / metabolism
  • T-Lymphocytes / immunology
  • Virus Diseases / immunology


  • Basic Helix-Loop-Helix Transcription Factors
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • endothelial PAS domain-containing protein 1
  • Oxygen