Complement C1q chemoattracts human dendritic cells and enhances migration of mature dendritic cells to CCL19 via activation of AKT and MAPK pathways.
Dendritic cells (DC) and complement are both important effectors in innate immunity, and also potent linkers between innate immunity and adaptive immunity. As key components of innate immunity, various bioactive complement components produced at the inflammatory sites have been found to be able to regulate functions of DC. It is well known that migration of DC to the peripheral inflammatory sites benefits the recognition and uptake of invading pathogens by DC as antigen-presenting cells, and DC migration to secondary lymphatic tissues benefits the priming and activation of T cells. However, up to date, little is known about the underlying signaling mechanisms for the regulation of DC migration by the multifunctional molecule C1q, the first member of classical pathway. In this study, we show that C1q mediates the chemotaxis and transendothelial migration of immature MoDC. Additionally, C1q significantly enhances the chemotaxis of LPS-induced mature DC to CCL19 via upregulation of CCR7 expression. Activation of PI3K/AKT, ERK and JNK pathways is required for the chemotaxis of immature DC to C1q, meanwhile activation of AKT and P38 pathways is required for the C1q-mediated enhancement of mature DC chemotaxis to CCL19. Therefore, our results suggest that C1q, actively produced and accumulated at the inflammatory sites, can directly chemoattract immature DC from blood to peripheral inflammatory tissues, and promotes the migration of mature DC to secondary lymph organs via activation of AKT and MAPK pathways, thus outlining new way for favoring the link of innate immunity to adaptive immunity.
Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai 200433, China.
Shuxun
S
Liu
Jiang
J
Wu
Ting
T
Zhang
Baohua
B
Qian
Pingping
P
Wu
Li
L
Li
Yizhi
Y
Yu
Xuetao
X
Cao
D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D054415:Chemokine CCL19 / Q000276:immunology*; D015922:Complement C1q / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology
C515460:CCL19 protein, human; D054415:Chemokine CCL19; D015922:Complement C1q; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases