Chi3l1, also known as chitinase-3-like protein 1 or YKL-40, belongs to glycoside hydrolase family 18. It binds to chitin, heparin, and hyaluronic acid, and is involved in various biological processes such as tissue injury, inflammation, repair, and remodeling. It plays a role in multiple signaling pathways and has been associated with numerous diseases [4]. Genetic models, especially KO/CKO mouse models, are valuable for studying its function.

In a PyMT breast cancer model, Chi3l1 ablation led to an anti-tumor immune response, increased T cell infiltration, and a delayed tumor onset, suggesting it promotes T cell exclusion in triple-negative breast cancer by inducing neutrophil extracellular traps [1]. In an APP/PS1 mouse model of Alzheimer's disease, Chi3l1 deletion decreased amyloid plaque burden, indicating it may suppress glial phagocytic activation and promote amyloid accumulation [2]. In multiple sclerosis-related studies, astrocytic deletion of Chi3l1 mitigated neurogenic deficits and cognitive dysfunction in a demyelinated hippocampus model [3].

In conclusion, Chi3l1 is a key factor in inflammation, tissue repair, and disease-related processes. Gene knockout mouse models have revealed its role in cancer, neurodegenerative diseases like Alzheimer's disease, and multiple sclerosis, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Taifour, Tarek, Attalla, Sherif Samer, Zuo, Dongmei, Park, Morag, Muller, William J. 2023. The tumor-derived cytokine Chi3l1 induces neutrophil extracellular traps that promote T cell exclusion in triple-negative breast cancer. In Immunity, 56, 2755-2772.e8. doi:10.1016/j.immuni.2023.11.002. https://pubmed.ncbi.nlm.nih.gov/38039967/

2. Lananna, Brian V, McKee, Celia A, King, Melvin W, Cruchaga, Carlos, Musiek, Erik S. . Chi3l1/YKL-40 is controlled by the astrocyte circadian clock and regulates neuroinflammation and Alzheimer's disease pathogenesis. In Science translational medicine, 12, . doi:10.1126/scitranslmed.aax3519. https://pubmed.ncbi.nlm.nih.gov/33328329/

3. Song, Yanna, Jiang, Wei, Afridi, Shabbir Khan, Qiu, Wei, Tang, Changyong. 2024. Astrocyte-derived CHI3L1 signaling impairs neurogenesis and cognition in the demyelinated hippocampus. In Cell reports, 43, 114226. doi:10.1016/j.celrep.2024.114226. https://pubmed.ncbi.nlm.nih.gov/38733586/

4. Zhao, Ting, Su, Zhongping, Li, Yingchang, Zhang, Xiaoren, You, Qiang. 2020. Chitinase-3 like-protein-1 function and its role in diseases. In Signal transduction and targeted therapy, 5, 201. doi:10.1038/s41392-020-00303-7. https://pubmed.ncbi.nlm.nih.gov/32929074/