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OSCAR‐collagen signaling in monocytes plays a proinflammatory role and may contribute to the pathogenesis of rheumatoid arthritis
Author(s) -
Schultz Heidi S.,
Guo Li,
Keller Pernille,
Fleetwood Andrew J.,
Sun Mingyi,
Guo Wei,
Ma Chunyan,
Hamilton John A.,
Bjørkdahl Olle,
Berchtold Martin W.,
Panina Svetlana
Publication year - 2016
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201545986
Subject(s) - proinflammatory cytokine , pathogenesis , monocyte , immunology , biology , rheumatoid arthritis , microbiology and biotechnology , inflammation
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‐α 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.