Cxcl15, also known as Lungkine, is a chemokine that plays significant roles in hematopoiesis and the regulation of immune cell behavior. It has been associated with pathways related to cell cycling regulation and immune cell recruitment. Cxcl15 is expressed in many bone marrow progenitor and other cell types, and its functions are important for maintaining normal physiological and immune responses [1].

Studies on Cxcl15 -/- mice revealed that this gene acts as a negative regulator of the cell cycling of multi-cytokine-stimulated bone marrow and spleen hematopoietic progenitor cells (CFU-GM, BFU-E, and CFU-GEMM) in vivo. Recombinant murine Cxcl15 decreased the numbers of functional HPCs during ex-vivo culture, and through S-Phase specific actions, suppressed in vitro colony formation of multiple types of mouse HPCs [1]. In prostate cancer, castration led to increased expression of Cxcl15 in prostate epithelial cells, which drove intratumoral infiltration of tumor-promoting polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Blocking IL-8 signaling (Cxcl15 is the probable murine homolog of human IL-8) genetically or pharmacologically largely abrogated this infiltration [2]. Tumor-derived OBP2A promotes prostate cancer castration resistance by catching survival factors like CXCL15, enhancing MDSC infiltration into the tumor microenvironment [3].

In conclusion, Cxcl15 is crucial for negatively regulating the proliferation of hematopoietic progenitor cells. In disease areas, especially in prostate cancer, Cxcl15 is involved in promoting tumor-associated myeloid cell infiltration, which contributes to cancer progression and the development of castration resistance. The study of Cxcl15 using gene knockout mouse models has provided valuable insights into its functions in normal and diseased biological processes.