Clec10a-KO Mouse

Clec10a, also known as macrophage galactose-type lectin (MGL1/CD301a), is a C-type lectin receptor. It belongs to the large family of C-type lectin receptors which are carbohydrate-binding proteins requiring Ca2+ to bind a ligand. Clec10a is involved in immune responses, including initiation of TH1, TH2, and TH17 immune responses and induction of tolerance in naïve T cells [2]. It has a unique recognition profile of glycan antigens with terminal N-Acetylgalactosamine residues [3].

NC/Nga mice carrying a stop-gain mutation in Clec10a are more susceptible to house dust mite (HDM)-induced dermatitis. Repair of this mutation using CRISPR-Cas9 system ameliorated HDM-induced dermatitis, and Clec10a-/-mice on the C57BL/6J background also showed exacerbated HDM-induced dermatitis. Clec10a expressed on skin macrophages inhibits HDM-induced Toll-like receptor 4 (TLR4)-mediated inflammatory cytokine production [1]. In the tumor microenvironment, while CLEC10A expression allows for precise targeting of cDC2 and DC3 for cancer treatment, its signaling has also been associated with anti-inflammatory responses that may promote tumor growth [3]. In lung adenocarcinoma, breast cancer, and head and neck squamous cell carcinoma, lower CLEC10A expression is associated with worse outcomes, and its expression is correlated with tumor-infiltrating immune cells [4,5,6].

In conclusion, Clec10a plays a crucial role in immune-related biological processes, especially in maintaining skin homeostasis against inflammation associated with HDM-induced dermatitis. Gene knockout mouse models have revealed its function in disease conditions such as allergic dermatitis and cancer, highlighting its potential as a biomarker and therapeutic target in these disease areas.