Intestinal epithelial BLT1 promotes mucosal repair

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Abstract
Acute and chronic intestinal inflammation is associated with epithelial damage, resulting in mucosal wounds in the forms of erosions and ulcers in the intestinal tract. Intestinal epithelial cells (IECs) and immune cells in the wound milieu secrete cytokines and lipid mediators to influence repair. Leukotriene B 4 (LTB 4 ), a lipid chemokine, binds to its receptor BLT1 and promotes migration of immune cells to sites of active inflammation; however, a role for intestinal epithelial BLT1 during mucosal wound repair is not known. Here we report that BLT1 was expressed in IECs both in vitro and in vivo, where it functioned as a receptor not only for LTB 4 but also for another ligand, resolvin E1. Intestinal epithelial BLT1 expression was increased when epithelial cells were exposed to an inflammatory microenvironment. Using human and murine primary colonic epithelial cells, we reveal that the LTB 4 /BLT1 pathway promoted epithelial migration and proliferation leading to accelerated epithelial wound repair. Furthermore, in vivo intestinal wound repair experiments in BLT1-deficient mice and bone marrow chimeras demonstrated an important contribution of epithelial BLT1 during colonic mucosal wound repair. Taken together, our findings show a potentially novel prorepair in IEC mechanism mediated by BLT1 signaling.
Funding Information
  • Norges Idrettshøgskole (DK055679,DK059888,DK089763,K061739,DK079392,DK072564)
  • University of Michigan Center for Gastrointestinal Research (P30DK034933)
  • Crohn's and Colitis Foundation (544599)
  • Japan Society for the Promotion of Science (JP17KK0166,18K06698,21K06593)
  • Moonshot R&D Program (PMJMS2021)

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