TY - JOUR
T1 - TARM1 contributes to development of arthritis by activating dendritic cells through recognition of collagens
AU - Yabe, Rikio
AU - Chung, Soo Hyun
AU - Murayama, Masanori A.
AU - Kubo, Sachiko
AU - Shimizu, Kenji
AU - Akahori, Yukiko
AU - Maruhashi, Takumi
AU - Seno, Akimasa
AU - Kaifu, Tomonori
AU - Saijo, Shinobu
AU - Iwakura, Yoichiro
N1 - Funding Information:
This work is supported by the Science and Technology Research Promotion Program for Agriculture, Forestry, Fisheries and Food Industry (to Y.I.), Grand-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (24220011 to Y.I.), and Grant-in-Aid for JSPS Fellows (11J09956 to R.Y.).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-020-20307-9
DO - 10.1038/s41467-020-20307-9
M3 - Article
C2 - 33397982
AN - SCOPUS:85098670359
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 94
ER -