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If it’s not one thing, HIF’s another: immunoregulation by hypoxia inducible factors in disease
Author(s) -
Hammond Ffion R.,
Lewis Amy,
Elks Philip M.
Publication year - 2020
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15476
Subject(s) - innate immune system , hypoxia inducible factors , immune system , inflammation , transcription factor , immunology , myeloid , biology , downregulation and upregulation , hypoxia (environmental) , disease , microbiology and biotechnology , myeloid cells , cell , immunity , cancer research , medicine , chemistry , pathology , genetics , organic chemistry , oxygen , gene
Hypoxia‐inducible factors (HIFs) have emerged in recent years as critical regulators of immunity. Localised, low oxygen tension is a hallmark of inflamed and infected tissues. Subsequent myeloid cell HIF stabilisation plays key roles in the innate immune response, alongside emerging oxygen‐independent roles. Manipulation of regulatory proteins of the HIF transcription factor family can profoundly influence inflammatory profiles, innate immune cell function and pathogen clearance and, as such, has been proposed as a therapeutic strategy against inflammatory diseases. The direction and mode of HIF manipulation as a therapy are dictated by the inflammatory properties of the disease in question, with innate immune cell HIF reduction being, in general, advantageous during chronic inflammatory conditions, while upregulation of HIF is beneficial during infections. The therapeutic potential of targeting myeloid HIFs, both genetically and pharmacologically, has been recently illuminated in vitro and in vivo , with an emerging range of inhibitory and activating strategies becoming available. This review focuses on cutting edge findings that uncover the roles of myeloid cell HIF signalling on immunoregulation in the contexts of inflammation and infection and explores future directions of potential therapeutic strategies.