Discoidin domain receptor 2 is involved in the activation of bone marrow-derived dendritic cells caused by type I collagen.
Discoidin domain receptors (DDRs), DDR1 and DDR2, are non-integrin receptor tyrosine kinases for collagen in many cell types. In this study, we investigated the contributions of DDRs to the activation of mouse bone marrow-derived dendritic cells (DCs) by type I collagen (ColI). Our data showed that transcript and protein of DDR2 were expressed constitutively in immature DCs and upregulated in TNF-alpha-stimulated mature DCs. ColI treatment induced DDR2 phosphorylation and subsequently induced the upregulation of IL-12 production, CD86 expression, and antigen uptake activity by immature DCs. Depletion of DDR2 by specific siRNA attenuated significantly an increase in expression of IL-12 and CD86 in ColI-treated DCs. Additionally, DDR2-ColI interaction upregulated the ability of mature DCs to activate allogeneic T cells. These findings suggest that DDR2 is a critical collagen receptor for DC activation and that DDR2-collagen interaction plays an important role in the functional capacity of DCs regulating immune responses.
Lee
Ji-Eun
JE
Department of Immunology, Chonbuk National University Medical School, Jeonbuk 561-180, Republic of Korea.
Kang
Chon-Sik
CS
Guan
Xiu-Ying
XY
Kim
Beom-Tae
BT
Kim
Sang-Hyun
SH
Lee
Young-Mi
YM
Moon
Woo-Sung
WS
Kim
Dae-Ki
DK
D000818:Animals; D051940:B7-2 Antigen / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D024042:Collagen Type I / Q000494:pharmacology*; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D000070818:Discoidin Domain Receptors; D005260:Female; D018664:Interleukin-12 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D051940:B7-2 Antigen; D024042:Collagen Type I; D011975:Receptors, Mitogen; D018664:Interleukin-12; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases