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A New Role for Myeloid HO-1 in the Innate to Adaptive Crosstalk and Immune Homeostasis

  • Vasiliki Koliaraki
  • George Kollias
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 780)

Abstract

Increasing evidence supports the presence of a dynamic crosstalk between innate and adaptive immunity with a pivotal role played by pathways governing innate immune responses. TLRs (Toll-like receptors) and RLHs (retinoic acid-inducible gene I [RIG-I]-like helicases) are known to play a key role in these processes. A molecule of high significance in the protection against innate and adaptive immune aberrations is heme oxygenase 1 (HO-1). HO-1 is a microsomal enzyme that catalyses the degradation of heme to iron, carbon monoxide and bilirubin. These by-products appear to be the key mediators of its anti-­inflammatory and cytoprotective action, mainly through the downregulation of pro-inflammatory and upregulation of anti-inflammatory molecules. Recent data from our lab support the presence of an additional direct effect of myeloid HO-1 on innate immune conditioning, and more specifically on the TLR3/TLR4/RIG-I pathway. In myeloid cells, HO-1 forms a complex with the transcription factor IRF3 (Interferon regulating factor 3) and is required for IRF3 phosphorylation and consequent type-I interferon and chemokine gene induction. Myeloid HO-1–deficient mice show reduced expression of IRF3 target genes and altered responses to infectious and organ-specific auto-immune diseases. This new frame of understanding HO-1 function should also be important for the future design of novel interventions differentially targeting the enzymatic versus the IRF3 modulating properties of HO-1.

Keywords

Heme Oxygenase Myeloid Differentiation Primary Response Gene Transcription Factor IRF3 Watanabe Heritable Hyperlipidemic Rabbit IRF3 Pathway 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This work was supported by the seventh FP European Commission programs MASTERSWITCH (223404) and INFLACARE (223151).

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© Springer Science+Businees Media, LLC 2011

Authors and Affiliations

  1. 1.Biomedical Sciences Research Center “Al. Fleming”Institute of ImmunologyVariGreece

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