CXCL17 is the last described chemokine, which is abundantly and specifically expressed in mucosal sites [1]. It is thought to potentially exhibit chemotactic, anti-inflammatory, and antimicrobial activities under multiple biological conditions, and may be involved in processes like recruiting myeloid cells, regulating angiogenesis, and defending against pathogenic microorganisms [4]. Its receptor is still not well-determined, though GPR35 has been suggested as a putative receptor, though this has been questioned [3].

In a mouse model of liver ischemia-reperfusion injury, endothelial YAP/TEAD1-CXCL17 signaling was found to recruit myeloid-derived suppressor cells (MDSCs), which alleviated liver IRI-induced inflammation and damage by inhibiting M1 macrophage polarization [2]. In a mouse model of aerosol infection with the hypervirulent Mycobacterium tuberculosis HN878 strain, CXCL17 production increased in the lung during acute and chronic stages of infection, but CXCL17-/-mice were not more susceptible to TB than wild-type animals, suggesting a dispensable role during pulmonary TB [6]. In C57BL/6 male mice exposed to diesel exhaust emissions (DEE), AAV5-CXCL17 enhanced macrophage recruitment and clearance of DEE in the lungs, improving respiratory parameters, airway injury, and airway remodeling [5].

In conclusion, CXCL17 appears to play roles in inflammation-related processes such as liver ischemia-reperfusion injury, DEE-induced lung damage, and potentially in anti-microbial defense during tuberculosis infection. The use of gene knockout mouse models in these studies has provided insights into the specific functions of CXCL17 in these disease-relevant biological processes, highlighting its potential as a therapeutic target in certain disease areas.

References:

1. Xiao, Shiyu, Xie, Wenhui, Zhou, Liya. 2020. Mucosal chemokine CXCL17: What is known and not known. In Scandinavian journal of immunology, 93, e12965. doi:10.1111/sji.12965. https://pubmed.ncbi.nlm.nih.gov/32869346/

2. Zhang, Sitong, Sun, Zhongquan, Chen, Zhenhua, Ding, Yuan, Wang, Weilin. 2024. Endothelial YAP/TEAD1-CXCL17 signaling recruits myeloid-derived suppressor cells against liver ischemia-reperfusion injury. In Hepatology (Baltimore, Md.), 81, 888-902. doi:10.1097/HEP.0000000000000773. https://pubmed.ncbi.nlm.nih.gov/38407233/

3. Giblin, Sean Patrick, Pease, James Edward. 2023. What defines a chemokine? - The curious case of CXCL17. In Cytokine, 168, 156224. doi:10.1016/j.cyto.2023.156224. https://pubmed.ncbi.nlm.nih.gov/37210967/

4. Hashemi, Seyyede Fatemeh, Khorramdelazad, Hossein. 2022. The cryptic role of CXCL17/CXCR8 axis in the pathogenesis of cancers: a review of the latest evidence. In Journal of cell communication and signaling, 17, 409-422. doi:10.1007/s12079-022-00699-7. https://pubmed.ncbi.nlm.nih.gov/36352331/

5. Yin, Yize, Mu, Chaohui, Wang, Jiahui, Li, Qinghai, Han, Wei. 2023. CXCL17 Attenuates Diesel Exhaust Emissions Exposure-Induced Lung Damage by Regulating Macrophage Function. In Toxics, 11, . doi:10.3390/toxics11080646. https://pubmed.ncbi.nlm.nih.gov/37624152/

6. Choreño-Parra, José Alberto, Dunlap, Micah D, Swanson, Rosemary, Zúñiga, Joaquín, Khader, Shabaana A. 2021. CXCL17 Is Dispensable during Hypervirulent Mycobacterium tuberculosis HN878 Infection in Mice. In ImmunoHorizons, 5, 752-759. doi:10.4049/immunohorizons.2100048. https://pubmed.ncbi.nlm.nih.gov/34561226/