TARM1 contributes to development of arthritis by activating dendritic cells through recognition of collagens

Rikio Yabe, Soo-Hyun Chung, Masanori A. Murayama, Sachiko Kubo, Kenji Shimizu, Yukiko Akahori, Takumi Maruhashi, Akimasa Seno, Tomonori Kaifu, Shinobu Saijo () and Yoichiro Iwakura ()
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Rikio Yabe: Tokyo University of Science
Soo-Hyun Chung: Tokyo University of Science
Masanori A. Murayama: Tokyo University of Science
Sachiko Kubo: Tokyo University of Science
Kenji Shimizu: Tokyo University of Science
Yukiko Akahori: Chiba University
Takumi Maruhashi: Tokyo University of Science
Akimasa Seno: Tokyo University of Science
Tomonori Kaifu: Tokyo University of Science
Shinobu Saijo: Chiba University
Yoichiro Iwakura: Tokyo University of Science

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-020-20307-9

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