OSCAR-collagen signaling in monocytes plays a proinflammatory role and may contribute to the pathogenesis of rheumatoid arthritis

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• 作者：Heidi S. Schultz ; Li Guo ; Pernille Keller ; Andrew J. Fleetwood ; Mingyi Sun ; Wei Guo ; Chunyan Ma ; John A. Hamilton ; Olle Bjø ; rkdahl ; Martin W. Berchtold and Svetlana Panina
• 关键词：Autoimmunity ; Collagen ; Inflammation ; Monocyte ; OSCAR ; Rheumatoid arthritis
• 刊名：European Journal of Immunology
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：46
• 期：4
• 页码：952-963
• 全文大小：800K
• ISSN：1521-4141

文摘

Osteoclast-associated receptor (OSCAR) is an activating receptor expressed by human myeloid cells. Collagen type I (ColI) and collagen type II (ColII) serve as ligands for OSCAR. OSCAR-collagen interaction stimulates RANK-dependent osteoclastogenesis. We have recently reported that OSCAR promotes functional maturation of monocyte-derived dendritic cells. OSCAR is upregulated on monocytes from rheumatoid arthritis (RA) patients with active disease, and these monocytes show an increased proosteoclastogenic potential. In the current study, we have addressed a functional role for an OSCAR–collagen interaction on monocytes. We show that OSCAR-ColII signaling promoted the survival of monocytes. Moreover, ColII stimulated the release of proinflammatory cytokines by monocytes from healthy donors, which could be completely blocked by an anti-OSCAR monoclonal antibody. Mononuclear cells from the synovial fluid of RA patients plated on ColII secreted TNF- and IL-8 in an OSCAR-dependent manner. Global RNA profiling showed that components of multiple signaling pathways relevant to RA pathogenesis are regulated at the transcriptional level by OSCAR in monocytes. Thus, OSCAR can play a proinflammatory role in monocyte-derived cells and may contribute crucially on multiple levels to RA pathogenesis.