Cmklr1, also known as ChemR23 or chemerin receptor 1, is a chemoattractant G protein-coupled receptor that responds to the adipokine chemerin. It is highly expressed in innate immune cells like macrophages and neutrophils. The signaling pathways of CMKLR1 can lead to both pro-and anti-inflammatory effects depending on ligands and physiological contexts. It is involved in various biological processes such as lipid metabolism, immune regulation, and adipocyte-related functions [4,6].

In mice, deficiency of IEC-specific Cmklr1 confers high susceptibility to microbiota-driven neutrophilic colon inflammation and subsequent tumorigenesis, due to reduced expression of lactoperoxidase (LPO) and consequent dysbiosis [1]. Cmklr1-KO mice used in the study of intestinal graft-versus-host disease (GvHD) showed worse survival and more severe GvHD, with the gastrointestinal tract being mostly affected, characterized by neutrophil infiltration and tissue damage [2]. In clear cell renal cell carcinoma (ccRCC), genetic and pharmacologic suppression of Cmklr1 suppressed lipid formation and induced cell death, impeding ccRCC growth [3]. In a murine model of cutaneous Staphylococcus aureus infection, lack of the chemerin/Cmkrl1 axis increased neutrophil-mediated host defense, while chemerin overexpression exacerbated the infection [5].

In conclusion, Cmklr1 plays crucial roles in immune regulation, lipid metabolism, and host-pathogen interactions. Studies using Cmklr1 KO mouse models have revealed its significance in diseases such as colitis, GvHD, ccRCC, and cutaneous infections, providing insights into potential therapeutic targets for these conditions.