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Publication : Formyl peptide receptor 2 regulates monocyte recruitment to promote intestinal mucosal wound repair.

First Author  Birkl D Year  2019
Journal  FASEB J Volume  33
Issue  12 Pages  13632-13643
PubMed ID  31585047 Mgi Jnum  J:293632
Mgi Id  MGI:6453043 Doi  10.1096/fj.201901163R
Citation  Birkl D, et al. (2019) Formyl peptide receptor 2 regulates monocyte recruitment to promote intestinal mucosal wound repair. FASEB J 33(12):13632-13643
abstractText  Mucosal wound repair is coordinated by dynamic crosstalk between endogenous and exogenous mediators and specific receptors on epithelial cells and infiltrating immune cells. One class of such receptor-ligand pairs involves formyl peptide receptors (FPRs) that have been shown to influence inflammatory response and repair. Here we explored the role of murine Fpr2/3, an ortholog of human FPR2/receptor for lipoxin A4 (ALX), in orchestrating intestinal mucosal repair. Compared with wild-type (WT) mice, Fpr2/3(-/-) mice exhibited delayed recovery from acute experimental colitis and perturbed repair after biopsy-induced colonic mucosal injury. Decreased numbers of infiltrating monocytes were observed in healing wounds from Fpr2/3(-/-) mice compared with WT animals. Bone marrow transplant experiments revealed that Fpr2/3(-/-) monocytes showed a competitive disadvantage when infiltrating colonic wounds. Moreover, Fpr2/3(-/-) monocytes were defective in chemotactic responses to the chemokine CC chemokine ligand (CCL)20, which is up-regulated during early phases of inflammation. Analysis of Fpr2/3(-/-) monocytes revealed altered expression of the CCL20 receptor CC chemokine receptor (CCR)6, suggesting that Fpr2/3 regulates CCL20-CCR6-mediated monocyte chemotaxis to sites of mucosal injury in the gut. These findings demonstrate an important contribution of Fpr2/3 in facilitating monocyte recruitment to sites of mucosal injury to influence wound repair.-Birkl, D., O'Leary, M. N., Quiros, M., Azcutia, V., Schaller, M., Reed, M., Nishio, H., Keeney, J., Neish, A. S., Lukacs, N. W., Parkos, C. A., Nusrat, A. Formyl peptide receptor 2 regulates monocyte recruitment to promote intestinal mucosal wound repair.
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