Clec12a-KO Mouse

Clec12a, a C-type lectin receptor, has diverse functions. It is involved in immune regulation, such as controlling neutrophil response thresholds to avoid collateral damage [3]. It also participates in innate immune surveillance, interacting with ligands like monosodium urate crystals and mycolic acid to suppress immune responses [4,7].

In mice, Clec12a -/- develop severe colitis, dependent on the microbiota. This reveals its role in tempering gut inflammation and restricting the expansion of colitogenic commensals like Faecalibaculum rodentium [2]. In acute myeloid leukemia (AML), Clec12a is expressed on leukemic stem cells and blasts. Low expression on leukemic blasts is linked to poor prognosis, and its absence on normal hematopoietic stem and progenitor cells makes it an attractive target for immunotherapies [1,5]. In breast cancer cells, modulating Clec12a with artemisinin affects autophagy, inflammation, and apoptosis [6].

In conclusion, Clec12a plays crucial roles in immune regulation, gut microbiota control, and cancer-related processes. Gene knockout mouse models have been instrumental in uncovering its functions in colitis and its potential significance in AML, highlighting its importance in understanding disease mechanisms and developing novel therapies.

References:

1. Morsink, Linde M, Walter, Roland B, Ossenkoppele, Gert J. 2018. Prognostic and therapeutic role of CLEC12A in acute myeloid leukemia. In Blood reviews, 34, 26-33. doi:10.1016/j.blre.2018.10.003. https://pubmed.ncbi.nlm.nih.gov/30401586/

2. Chiaro, Tyson R, Bauer, Kaylyn M, Ost, Kyla S, Zac Stephens, W, Round, June L. 2023. Clec12a tempers inflammation while restricting expansion of a colitogenic commensal. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.03.16.532997. https://pubmed.ncbi.nlm.nih.gov/36993296/

3. McLeish, Kenneth R, Fernandes, Maria J. 2022. Understanding inhibitory receptor function in neutrophils through the lens of CLEC12A. In Immunological reviews, 314, 50-68. doi:10.1111/imr.13174. https://pubmed.ncbi.nlm.nih.gov/36424898/

4. Xu, Ying, Song, Dingka, Wang, Wei, Xia, Tie, Shi, Yan. 2023. Clec12a inhibits MSU-induced immune activation through lipid raft expulsion. In Life science alliance, 6, . doi:10.26508/lsa.202301938. https://pubmed.ncbi.nlm.nih.gov/37339805/

5. Li, Qiaoqiao, Liang, Chunyan, Xu, Xintong, Xing, Haizhou, Yu, Jifeng. 2022. CLEC12A plays an important role in immunomodulatory function and prognostic significance of patients with acute myeloid leukemia. In Leukemia & lymphoma, 63, 2136-2148. doi:10.1080/10428194.2022.2064986. https://pubmed.ncbi.nlm.nih.gov/35481814/

6. Chatterjee, Ranodeep, Shukla, Aditya, Chakrabarti, Kausiki, Chatterji, Urmi. 2023. CLEC12A sensitizes differentially responsive breast cancer cells to the anti-cancer effects of artemisinin by repressing autophagy and inflammation. In Frontiers in oncology, 13, 1242432. doi:10.3389/fonc.2023.1242432. https://pubmed.ncbi.nlm.nih.gov/38144525/

7. Mori, Shotaro, Nagae, Masamichi, Yamasaki, Sho. . Crystal structure of the complex of CLEC12A and an antibody that interferes with binding of diverse ligands. In International immunology, 36, 279-290. doi:10.1093/intimm/dxae006. https://pubmed.ncbi.nlm.nih.gov/38386511/