Center for Animal Disease Models, Research Institute for Biomedical Sciences (RIBS), Tokyo University of Science, Noda, Chiba, 278-0022, Japan.
Medical Mycobiology Research Center, Chiba University, Chiba, Chiba, 260-8673, Japan.
Nat Commun. 2021 Jan 4;12(1):94. doi: 10.1038/s41467-020-20307-9.
TARM1 is a member of the leukocyte immunoglobulin-like receptor family and stimulates macrophages and neutrophils in vitro by associating with FcRγ. However, the function of this molecule in the regulation of the immune system is unclear. Here, we show that Tarm1 expression is elevated in the joints of rheumatoid arthritis mouse models, and the development of collagen-induced arthritis (CIA) is suppressed in Tarm1 mice. T cell priming against type 2 collagen is suppressed in Tarm1 mice and antigen-presenting ability of GM-CSF-induced dendritic cells (GM-DCs) from Tarm1 mouse bone marrow cells is impaired. We show that type 2 collagen is a functional ligand for TARM1 on GM-DCs and promotes DC maturation. Furthermore, soluble TARM1-Fc and TARM1-Flag inhibit DC maturation and administration of TARM1-Fc blocks the progression of CIA in mice. These results indicate that TARM1 is an important stimulating factor of dendritic cell maturation and could be a good target for the treatment of autoimmune diseases.
TARM1 是白细胞免疫球蛋白样受体家族的成员，通过与 FcRγ 结合在体外刺激巨噬细胞和中性粒细胞。然而，该分子在免疫系统调节中的功能尚不清楚。在这里，我们表明 Tarm1 在类风湿关节炎小鼠模型的关节中表达上调，并且 Tarm1 小鼠中胶原诱导性关节炎 (CIA) 的发展受到抑制。Tarm1 小鼠中针对 2 型胶原的 T 细胞启动受到抑制，并且来自 Tarm1 小鼠骨髓细胞的 GM-CSF 诱导的树突状细胞 (GM-DC) 的抗原呈递能力受损。我们表明 2 型胶原是 GM-DC 上 TARM1 的功能性配体，并促进 DC 成熟。此外，可溶性 TARM1-Fc 和 TARM1-Flag 抑制 DC 成熟，并且 TARM1-Fc 的给药可阻止 CIA 在小鼠中的进展。这些结果表明 TARM1 是树突状细胞成熟的重要刺激因子，并且可能是治疗自身免疫性疾病的良好靶标。
