Clec4n-KO Mouse

Clec4n, also known as Dectin-2, is a C-type lectin receptor. It functions as a pattern-recognition receptor for fungi, some components of house dust mite (HDM) extract, and mannose-capped lipoarabinomannan (Man-LAM) of mycobacteria. It is involved in immune-related pathways such as the activation of NF-κB signaling axis and cytokine production. Genetic models, like Clec4n-deficient (Clec4n(-/-)) mice, are crucial for studying its functions [2,3,4,5].

In acute lung injury (ALI), knockdown of IGFBP7 reduced the infiltration of Clec4nhi neutrophils, indicating that Clec4nhi neutrophils may aggravate lung injury in an endothelial IGFBP7-dependent manner [1]. In experimental autoimmune encephalitis (EAE), Clec4n(-/-) mice were resistant to Man-LAM-induced EAE, while upon mycobacterial infection, these mice showed augmented lung pathology, demonstrating Dectin-2's role in host immunity against mycobacterial infection [2]. In HDM-induced allergic airway inflammation, Clec4n(-/-) mice had attenuated inflammation and decreased Th2 and Th17 cell differentiation, and Dectin-2 expressed on CD11b(+) dendritic cells (DCs) promoted this process [3]. Also, Clec4n(-/-) DCs had no fungal alpha-mannan-induced cytokine production, and Dectin-2 was mainly involved in Th17 cell differentiation induced by Candida albicans, suggesting its importance in host defense against this fungus [5].

In conclusion, Clec4n plays essential roles in various immune-related biological processes. The use of Clec4n KO mouse models has revealed its significance in diseases such as ALI, EAE, allergic airway inflammation, and fungal infections, providing valuable insights into the immune mechanisms underlying these conditions.

References:

1. Yu, Lin-Chao, He, Rui, Wang, Dao-Xin, Qi, Di. . Activated Clec4nhi Neutrophils Aggravate Lung Injury in an Endothelial IGFBP7-Dependent Manner. In American journal of respiratory cell and molecular biology, 71, 66-80. doi:10.1165/rcmb.2024-0017OC. https://pubmed.ncbi.nlm.nih.gov/38574235/

2. Yonekawa, Akiko, Saijo, Shinobu, Hoshino, Yoshihiko, Akashi, Koichi, Yamasaki, Sho. 2014. Dectin-2 is a direct receptor for mannose-capped lipoarabinomannan of mycobacteria. In Immunity, 41, 402-413. doi:10.1016/j.immuni.2014.08.005. https://pubmed.ncbi.nlm.nih.gov/25176311/

3. Norimoto, Ayako, Hirose, Koichi, Iwata, Arifumi, Iwakura, Yoichiro, Nakajima, Hiroshi. . Dectin-2 promotes house dust mite-induced T helper type 2 and type 17 cell differentiation and allergic airway inflammation in mice. In American journal of respiratory cell and molecular biology, 51, 201-9. doi:10.1165/rcmb.2013-0522OC. https://pubmed.ncbi.nlm.nih.gov/24588637/

4. Qu, Yulan, Ma, Xiaotian, Deng, Jiewen, Guo, Zhenhong, Bai, Chong. 2022. Dectin-2 promotes house dust mite-skewed Th2 response through the activation of cDC2s. In Cellular immunology, 378, 104558. doi:10.1016/j.cellimm.2022.104558. https://pubmed.ncbi.nlm.nih.gov/35717749/

5. Saijo, Shinobu, Ikeda, Satoshi, Yamabe, Keiko, Akira, Shizuo, Iwakura, Yoichiro. 2010. Dectin-2 recognition of alpha-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans. In Immunity, 32, 681-91. doi:10.1016/j.immuni.2010.05.001. https://pubmed.ncbi.nlm.nih.gov/20493731/