Cxcl15-KO Mouse

Cxcl15, also known as Lungkine, is a chemokine that belongs to the CXC chemokine family. It plays significant roles in hematopoiesis, immune regulation, and inflammation. Cxcl15 is involved in signaling pathways related to cell proliferation, chemotaxis, and immune cell recruitment [1,2,3].

Genetic models, especially knockout (KO) mouse models, have been instrumental in understanding Cxcl15's functions. Cxcl15 -/- mice show increased cycling of multi-cytokine-stimulated bone marrow and spleen hematopoietic progenitor cells, indicating that Cxcl15 acts as a negative regulator of cell cycling of these hematopoietic progenitor cells (HPCs) in vivo [1]. In pancreatic ductal adenocarcinoma, CRIP1 upregulation leads to transcriptional activation of CXCL1/5, facilitating the chemotactic migration of myeloid-derived suppressor cells (MDSCs) [2]. In prostate cancer, castration increases the expression of Cxcl15, which drives intratumoral infiltration of tumor-promoting polymorphonuclear MDSCs [3].

In summary, Cxcl15 has important functions in hematopoiesis and immune-related processes. KO mouse models have revealed its role in regulating HPC proliferation and its implications in cancer-related immune evasion, such as in pancreatic and prostate cancers. Understanding Cxcl15's functions can potentially provide new insights into the mechanisms of these diseases and lead to the development of novel therapeutic strategies [1,2,3].

References:

1. Broxmeyer, Hal E, Cooper, Scott H, Ropa, James. 2021. CXCL15/Lungkine has suppressive activity on proliferation and expansion of multi-potential, erythroid, granulocyte and macrophage progenitors in S-phase specific manner. In Blood cells, molecules & diseases, 91, 102594. doi:10.1016/j.bcmd.2021.102594. https://pubmed.ncbi.nlm.nih.gov/34520986/

2. Liu, Xiaomeng, Tang, Rong, Xu, Jin, Yu, Xianjun, Shi, Si. 2023. CRIP1 fosters MDSC trafficking and resets tumour microenvironment via facilitating NF-κB/p65 nuclear translocation in pancreatic ductal adenocarcinoma. In Gut, 72, 2329-2343. doi:10.1136/gutjnl-2022-329349. https://pubmed.ncbi.nlm.nih.gov/37541772/

3. Lopez-Bujanda, Zoila A, Haffner, Michael C, Chaimowitz, Matthew G, De Marzo, Angelo M, Drake, Charles G. 2021. Castration-mediated IL-8 promotes myeloid infiltration and prostate cancer progression. In Nature cancer, 2, 803-818. doi:10.1038/s43018-021-00227-3. https://pubmed.ncbi.nlm.nih.gov/35122025/

4. Asanuma, Kanna, Yokota, Seiji, Chosa, Naoyuki, Satoh, Kazuro, Ishisaki, Akira. 2022. Hydrogen peroxide-induced oxidative stress promotes expression of CXCL15/Lungkine mRNA in a MEK/ERK-dependent manner in fibroblast-like synoviocytes derived from mouse temporomandibular joint. In Journal of oral biosciences, 65, 97-103. doi:10.1016/j.job.2022.12.002. https://pubmed.ncbi.nlm.nih.gov/36584898/