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Immunologic Research

, Volume 55, Issue 1–3, pp 58–70 | Cite as

Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function

  • Eóin N. McNamee
  • Darlynn Korns Johnson
  • Dirk Homann
  • Eric T. ClambeyEmail author
Immunology in Colorado

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.

Keywords

T cell Oxygen Hypoxia Hypoxia-inducible factor Metabolism 

Abbreviations

EPO

Erythyropoietin

FoxP3

Forkhead box P3

HIF

Hypoxia inducible factor

HRE

Hypoxia response element

IBD

Inflammatory bowel disease

IEL

Intraepithelial lymphocyte

kPa

Kilopascal

mm Hg

Millimeter of mercury

PHD

Prolyl hydroxylase

TCR

T cell receptor

Tregs

Regulatory T cells

VEGF

Vascular endothelial growth factor

VHL

von Hippel-Lindau

Notes

Acknowledgments

The authors were funded in part by National Institutes of Health grants R01 AI093637-01A1 and U19 AI050864 P&F to DH and a Crohn’s and Colitis Foundation of America grant to ENM. The authors thank Dr. Holger Eltzschig for critical discussion and ongoing support, and Dr. Linda van Dyk for critical review.

Conflict of interest

The authors declare no competing financial interests.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Eóin N. McNamee
    • 1
  • Darlynn Korns Johnson
    • 1
    • 2
  • Dirk Homann
    • 1
    • 2
  • Eric T. Clambey
    • 1
    Email author
  1. 1.Mucosal Inflammation Program, Department of Anesthesiology, School of MedicineUniversity of Colorado DenverAuroraUSA
  2. 2.Integrated Department of Immunology, National Jewish HealthUniversity of Colorado DenverAuroraUSA

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