Maturation of dendritic cells abrogates C1q production in vivo and in vitro.
Dendritic cells (DCs) and complement are essential components of the innate immune system. Immature DCs (immDCs) and mature DCs (mDCs) can migrate to lymphoid areas inducing, respectively, tolerance and immune responses. Primary deficiency of complement component C1q (C1q) leads to autoimmunity, suggesting a role in the maintenance of tolerance. In the present study, we investigated the production of C1q by immDCs, mDCs, and macrophages. We demonstrated that monocyte-derived and CD34(+)-derived interstitial DCs are a rich source of C1q. C1q produced by immDCs is functionally active in complement activation and binding to apoptotic cells. The production of C1q is completely down-regulated upon DC maturation in vitro. Moreover, we found that DC differentiation in the presence of interferon-alpha (IFN-alpha) accelerated DC maturation and strongly impaired overall C1q production. Finally, we demonstrated the presence, in significant numbers, of DC-SIGN(+)/C1q(+) cells in T-cell areas of tonsils, next to DC-LAMP(+) mDCs lacking C1q. We conclude from these results that immDC, a cell with tolerogenic properties, is a rich source of active C1q in vitro and in vivo, which is down-regulated on maturation. Therefore, immDCs may be considered an additional source of C1q in humans.
Castellano
Giuseppe
G
Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands.
Woltman
Andrea M
AM
Nauta
Alma J
AJ
Roos
Anja
A
Trouw
Leendert A
LA
Seelen
Marc A
MA
Schena
Francesco Paolo
FP
Daha
Mohamed R
MR
van Kooten
Cees
C
D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D003167:Complement Activation; D015922:Complement C1q / Q000032:analysis / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D014066:Palatine Tonsil / Q000166:cytology; D010587:Phagocytosis; D013997:Time Factors
D016898:Interferon-alpha; D015922:Complement C1q