Formyl peptide receptor 2 is a potential biomarker and therapeutic target for inflammatory bowel disease.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is characterized by limited treatment options and a therapeutic ceiling. Failure to resolve inflammation is the key driver of disease progression. Formyl peptide receptor 2 (FPR2/ALX), a pivotal mediator of inflammation resolution, has emerged as a promising therapeutic target. In this study, we investigated the expression patterns of FPR2 and clinical relevance in myeloid and lymphoid cells of active IBD patients. By analyzing transcriptomic and single-cell RNA-sequencing data from the GEO database, we revealed aberrant expression of FPR2 and its associated genes in colonic mucosa of IBD patients. We found that FPR2/ALX was highly expressed in the colonic mucosa of UC and CD patients compared to non-IBD controls, strongly correlating with alterations in the MAPK pathway and myeloid cell composition. Notably, high mucosal FPR2/ALX levels were associated with poor response to anti-tumor necrosis factor-α (TNF-α) agent infliximab, and were predictive of disease status (AUC = 0.9143). To assess therapeutic potential, we established a dextran sulfate sodium (DSS)-induced colitis model in wild-type and Fpr2-silenced mice. The mice were orally treated with FPR2/ALX modulators Quin-C1 (QC1) and Quin-C7 (QC7) for 7 days. We showed that oral administration of QC1 or QC7 significantly reduced disease active index (DAI) in wild-type mice, whereas the therapeutic effects were markedly impaired in Fpr2-silenced mice. We conclude that FPR2/ALX may serve as a potential biomarker and therapeutic target for IBD.