Chil3, also known as chitinase-like protein 3 (and CHI3L1 in human), has diverse functions. It is involved in macrophage polarization, which is crucial for immune-related biological processes. In the context of inflammation regulation, Chil3 is associated with the IL-4-STAT6 signaling pathway [3]. It also appears to be related to the CX3CR1-mediated pathway in the context of liver ischemia-reperfusion injury [1].

In a study on liver ischemia-reperfusion injury, M2 macrophage-secreted Chil3 was shown to be an important effector downstream of CX3CR1 deficiency. Addition of CHIL3/CHI3L1 alone improved hepatocellular metabolism and reduced oxygen-glucose deprivation/re-oxygenation-inflicted injuries in cultured mouse and human hepatocytes [1]. In another study, single-cell RNA-sequencing of tumor-bearing mice after different vaccination routes revealed that intratumoral monocytes expressing Chil3 were reduced after intravenous boost with a self-assembling nanoparticle vaccine, and in humans, the Chil3 + monocyte gene signature in CD16-monocytes was associated with worse outcomes [2]. Also, in sepsis-induced acute lung injury, deletion of Padi2 and Padi4 reduced Nlrp3 + proinflammatory macrophages and fostered Chil3 + myeloid cell differentiation into anti-inflammatory macrophages, highlighting the role of Chil3 in inflammation resolution [4].

In conclusion, Chil3 plays essential roles in macrophage-related immune responses, metabolism regulation in the liver, and in the tumor microenvironment. Gene-knockout mouse models, such as the Cx3cr1 KO mice in the liver injury study, have been crucial in revealing these functions. These findings suggest that Chil3 could be a potential target for treating diseases related to liver ischemia-reperfusion injury, certain cancers, and sepsis-induced acute lung injury.