TARM1, also known as T cell-interacting, activating receptor on myeloid cells 1, is a member of the leukocyte immunoglobulin-like receptor family. It associates with FcRγ and is involved in stimulating macrophages, neutrophils, and dendritic cells. TARM1 participates in multiple biological processes, such as immune cell activation and cytokine secretion, and is relevant to pathways like NF-κB, which are associated with inflammation [2,4].

In gene-knockout mouse models, Tarm1-/-mice showed suppressed development of collagen-induced arthritis (CIA), with impaired T cell priming against type 2 collagen and antigen-presenting ability of GM-CSF-induced dendritic cells [2]. In macrophage-specific autophagy-deficient (atg5-/-) mice, deletion of atg5 led to upregulated TARM1 protein expression, promoting renal inflammation in acute kidney injury (AKI), while TARM1 inhibition suppressed the inflammatory response [1]. In a mouse colitis model, knockdown of Tarm1 in RAW264.7 cells inhibited lipopolysaccharide (LPS)-induced M1 polarization and attenuated barrier damage in co-cultured intestinal epithelial cells [3]. In a mouse model of Mycobacterium tuberculosis infection, administration of TARM-1 blocking peptide increased bacterial load and lung pathology, associated with decreased macrophage activation and IFN-γ production by T cell [5].

In conclusion, TARM1 plays essential roles in immune-related biological processes. Studies using Tarm1 KO mouse models have revealed its significance in diseases like arthritis, AKI, colitis, and tuberculosis. These findings provide potential therapeutic targets for these disease areas.

References:

1. Huang, Xiao-Rong, Ye, Lin, An, Ning, Yang, Chen, Liu, Hua-Feng. 2024. Macrophage autophagy protects against acute kidney injury by inhibiting renal inflammation through the degradation of TARM1. In Autophagy, 21, 120-140. doi:10.1080/15548627.2024.2393926. https://pubmed.ncbi.nlm.nih.gov/39193910/

2. Yabe, Rikio, Chung, Soo-Hyun, Murayama, Masanori A, Saijo, Shinobu, Iwakura, Yoichiro. 2021. TARM1 contributes to development of arthritis by activating dendritic cells through recognition of collagens. In Nature communications, 12, 94. doi:10.1038/s41467-020-20307-9. https://pubmed.ncbi.nlm.nih.gov/33397982/

3. Zhang, Kun, Xu, Lingfen, Guo, Jing. 2024. Tarm1 may affect colitis by regulating macrophage M1 polarization in a mouse colitis model. In Pediatric research, , . doi:10.1038/s41390-024-03640-3. https://pubmed.ncbi.nlm.nih.gov/39487321/

4. Radjabova, Valeria, Mastroeni, Piero, Skjødt, Karsten, Trowsdale, John, Barrow, Alexander David. 2015. TARM1 Is a Novel Leukocyte Receptor Complex-Encoded ITAM Receptor That Costimulates Proinflammatory Cytokine Secretion by Macrophages and Neutrophils. In Journal of immunology (Baltimore, Md. : 1950), 195, 3149-59. doi:10.4049/jimmunol.1401847. https://pubmed.ncbi.nlm.nih.gov/26311901/

5. Li, Xingyu, Wang, Manni, Ming, Siqi, Gong, Sitang, Wu, Yongjian. 2021. TARM-1 Is Critical for Macrophage Activation and Th1 Response in Mycobacterium tuberculosis Infection. In Journal of immunology (Baltimore, Md. : 1950), 207, 234-243. doi:10.4049/jimmunol.2001037. https://pubmed.ncbi.nlm.nih.gov/34183366/