TY - JOUR AU - Lin, Nan AU - Shay, Jessica E. S. AU - Xie, Hong AU - Lee, David S. M. AU - Skuli, Nicolas AU - Tang, Qiaosi AU - Zhou, Zilu AU - Azzam, Andrew AU - Meng, Hu AU - Wang, Haichao AU - FitzGerald, Garret A. AU - Simon, M. Celeste PY - 2018 M3 - Original Research TI - Myeloid Cell Hypoxia-Inducible Factors Promote Resolution of Inflammation in Experimental Colitis JO - Frontiers in Immunology UR - https://www.frontiersin.org/articles/10.3389/fimmu.2018.02565 VL - 9 SN - 1664-3224 N2 - 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. ER -