Immune modulation of human dendritic cells by complement.
Deficiency in complement proteins such as C1q is associated with the development of systemic lupus erythematosus (SLE). Here, we show that the differentiation of dendritic cells (DC) in the presence of C1q (C1qDC) gives rise to CD1a(+)/DC-SIGN(+) cells with high phagocytic capacity and low expression of CD80, CD83 and CD86. Further, when C1qDC were exposed to LPS, a significant reduction in the production of IL-6, TNF-alpha and IL-10 occurred with a limited up-regulation of CD80, CD83 and CD86. In addition, C1qDC were less responsive to activation by CD40L in terms of IL-12p70 secretion and CD86 expression. C1qDC showed an impaired ability to stimulate alloreactive T cells, with a reduced production of IFN-gamma. In conclusion, we have shown that C1q is a potent modulator of DC, resulting in cells characterized by an impaired capacity of cytokine production and an impaired up-regulation of costimulatory molecules, leading to a limited T cell response. Therefore, we hypothesize that, next to a pivotal role in the safe clearance of apoptotic cells, C1q regulates the threshold of DC activation and thereby prevents hyperactivation of the overall immune response.
Castellano
Giuseppe
G
Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
Woltman
Andrea M
AM
Schlagwein
Nicole
N
Xu
Wei
W
Schena
Francesco P
FP
Daha
Mohamed R
MR
van Kooten
Cees
C
D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D015922:Complement C1q / Q000502:physiology*; D003171:Complement Pathway, Classical / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D037181:Lectins, C-Type / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D015922:Complement C1q; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin