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

Rikio Yabe,Akimasa Seno,Kenji Shimizu,Sachiko Kubo,Tomonori Kaifu,Soo-Hyun Chung,Shinobu Saijo,Yoichiro Iwakura,Takumi Maruhashi,Masanori A Murayama,Yukiko Akahori

doi:10.1038/s41467-020-20307-9

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.

Highlights

TARM1 is a member of the leukocyte immunoglobulin-like receptor family and stimulates macrophages and neutrophils in vitro by associating with FcRγ
We investigated the role of TARM1 in the development of autoimmune arthritis using Tarm1–/– mice, in which the Tarm[1] gene exon 1 was replaced by enhanced green fluorescence protein (EGFP) and the neomycin-resistant gene by homologousrecombination techniques (Supplementary Fig. 1c–f)
In this report, we showed that the development of collagen-induced arthritis (CIA) is greatly suppressed in Tarm1–/– mice

Summary

Introduction

TARM1 is a member of the leukocyte immunoglobulin-like receptor family and stimulates macrophages and neutrophils in vitro by associating with FcRγ. 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. Some of LILR family members are expressed in myeloid cells, such as dendritic cells (DCs) and macrophages, and transduce activation or inhibitory signals into these cells[1,2,3]. Because these family members are closely associated with autoimmune diseases, the importance of these molecules in the homeostasis of the immune system is suggested[4,5,6]. Tarm[1] is expressed constitutively in bone marrow (BM)-derived granulocytes, monocytes, neutrophils, and granulocyte/macrophage colony-stimulating factor (GM-CSF)-induced DCs

Methods

Results

Conclusion