@ARTICLE{10.3389/fimmu.2018.02565, AUTHOR={Lin, Nan and Shay, Jessica E. S. and Xie, Hong and Lee, David S. M. and Skuli, Nicolas and Tang, Qiaosi and Zhou, Zilu and Azzam, Andrew and Meng, Hu and Wang, Haichao and FitzGerald, Garret A. and Simon, M. Celeste}, TITLE={Myeloid Cell Hypoxia-Inducible Factors Promote Resolution of Inflammation in Experimental Colitis}, JOURNAL={Frontiers in Immunology}, VOLUME={9}, YEAR={2018}, URL={https://www.frontiersin.org/articles/10.3389/fimmu.2018.02565}, DOI={10.3389/fimmu.2018.02565}, ISSN={1664-3224}, ABSTRACT={Colonic tissues in Inflammatory Bowel Disease (IBD) patients exhibit oxygen deprivation and activation of hypoxia-inducible factor 1α and 2α (HIF-1α and HIF-2α), which mediate cellular adaptation to hypoxic stress. Notably, macrophages and neutrophils accumulate preferentially in hypoxic regions of the inflamed colon, suggesting that myeloid cell functions in colitis are HIF-dependent. By depleting ARNT (the obligate heterodimeric binding partner for both HIFα subunits) in a murine model, we demonstrate here that myeloid HIF signaling promotes the resolution of acute colitis. Specifically, myeloid pan-HIF deficiency exacerbates infiltration of pro-inflammatory neutrophils and Ly6C+ monocytic cells into diseased tissue. Myeloid HIF ablation also hinders macrophage functional conversion to a protective, pro-resolving phenotype, and elevates gut serum amyloid A levels during the resolution phase of colitis. Therefore, myeloid cell HIF signaling is required for efficient resolution of inflammatory damage in colitis, implicating serum amyloid A in this process.} }