Collagen induces maturation of human monocyte-derived dendritic cells by signaling through osteoclast-associated receptor.
Osteoclast-associated receptor (OSCAR) is widely expressed on human myeloid cells. Collagen types (Col)I, II, and III have been described as OSCAR ligands, and ColII peptides can induce costimulatory signaling in receptor activator for NF-κB-dependent osteoclastogenesis. In this study, we isolated collagen as an OSCAR-interacting protein from the membranes of murine osteoblasts. We have investigated a functional outcome of the OSCAR-collagen interaction in human monocyte-derived dendritic cells (DCs). OSCAR engagement by ColI/II-induced activation/maturation of DCs is characterized by upregulation of cell surface markers and secretion of cytokines. These collagen-matured DCs (Col-DCs) were efficient drivers of allogeneic and autologous naive T cell proliferation. The T cells expanded by Col-DCs secreted cytokines with no clear T cell polarization pattern. Global RNA profiling revealed that multiple proinflammatory mediators, including cytokines and cytokine receptors, components of the stable immune synapse (namely CD40, CD86, CD80, and ICAM-1), as well as components of TNF and TLR signaling, are transcriptional targets of OSCAR in DCs. Our findings indicate the existence of a novel pathway by which extracellular matrix proteins locally drive maturation of DCs during inflammatory conditions, for example, within synovial tissue of rheumatoid arthritis patients, where collagens become exposed during tissue remodeling and are thus accessible for interaction with infiltrating precursors of DCs.
Biopharmaceutical Research Unit, Novo Nordisk A/S, 2760 Måløv, Denmark; Department of Biology, Copenhagen University, Copenhagen 2200, Denmark;
Heidi S
HS
Schultz
Biopharmaceutical Research Unit, Novo Nordisk A/S, 2760 Måløv, Denmark; Department of Biology, Copenhagen University, Copenhagen 2200, Denmark;
Louise M
LM
Nitze
Biopharmaceutical Research Unit, Novo Nordisk A/S, 2760 Måløv, Denmark;
Louise H
LH
Zeuthen
Biopharmaceutical Research Unit, Novo Nordisk A/S, 2760 Måløv, Denmark;
Pernille
P
Keller
Biopharmaceutical Research Unit, Novo Nordisk A/S, 2760 Måløv, Denmark;
Albrecht
A
Gruhler
Biopharmaceutical Research Unit, Novo Nordisk A/S, 2760 Måløv, Denmark;
Jesper
J
Pass
Novo Nordisk Research Center China, Beijing 102206, China; and.
Jianhe
J
Chen
Novo Nordisk Research Center China, Beijing 102206, China; and.
Li
L
Guo
Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
Andrew J
AJ
Fleetwood
Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
John A
JA
Hamilton
Department of Biology, Copenhagen University, Copenhagen 2200, Denmark;
Martin W
MW
Berchtold
Biopharmaceutical Research Unit, Novo Nordisk A/S, 2760 Måløv, Denmark; paninas007@gmail.com.
Svetlana
S
Panina
D000954:Antigens, Surface / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D018925:Chemokines / Q000096:biosynthesis; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism* / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D016130:Immunophenotyping; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000954:Antigens, Surface; D018925:Chemokines; D016207:Cytokines; D008024:Ligands; D016328:NF-kappa B; C512828:OSCAR protein, human; D011956:Receptors, Cell Surface; D003094:Collagen