The dendritic cell immunoreceptor (official gene symbol Clec4a2, called Dcir here) is a C-type lectin receptor expressed mainly in dendritic cells (DCs) that has a carbohydrate recognition domain in its extracellular portion and an immunoreceptor tyrosine–based inhibitory motif, which transduces negative signals into cells, in its cytoplasmic portion1. We found high Dcir expression in the joints of two mouse rheumatoid arthritis models2,3,4. Because the structural characteristics of Dcir suggest that it may have an immune regulatory role, and because autoimmune-related genes are mapped to the DCIR locus in humans, we generated Dcir−/− mice to learn more about the pathological roles of this molecule. We found that aged Dcir−/− mice spontaneously develop sialadenitis and enthesitis associated with elevated serum autoantibodies. Dcir−/− mice showed a markedly exacerbated response to collagen-induced arthritis. The DC population was expanded excessively in aged and type II collagen–immunized Dcir−/− mice. Upon treatment with granulocyte-macrophage colony–stimulating factor, Dcir−/− mouse–derived bone marrow cells (BMCs) differentiated into DCs more efficiently than did wild-type BMCs, owing to enhanced signal transducer and activator of transcription-5 phosphorylation. These observations indicate that Dcir is a negative regulator of DC expansion and has a crucial role in maintaining the homeostasis of the immune system.
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We thank all of the members of the laboratory for their excellent animal care. This research was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan and the Ministry of Health and Welfare of Japan. N.F. was supported by a fellowship from the Japan Society for the Promotion of Science.
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Fujikado, N., Saijo, S., Yonezawa, T. et al. Dcir deficiency causes development of autoimmune diseases in mice due to excess expansion of dendritic cells. Nat Med 14, 176–180 (2008). https://doi.org/10.1038/nm1697
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