title: C1q regulation of dendritic cell development from monocytes with distinct cytokine production and T cell stimulation.
abstract: The causative association of complement C1q deficiency with systemic lupus erythematosus (SLE), which inevitably involves the breakdown of tolerance, remains poorly explained. Its non-hepatic, macrophage and dendritic cell (DC) origin may be highly relevant. In tissues, C1q is produced by DCs and macrophages which deposits around these cells and we ask whether this pericellular form of C1q regulates DC development from monocytes. DCs cultured on immobilized C1q (C1q-DCs) show similar MHC, CD40, CD80, CD86, CD83 and CCR7 expression as normal DCs, but these cells exhibit increased phagocytosis of apoptotic cells and elevated IL-10 but reduced IL-12 and IL-23 production. Intracellularly, C1q-DCs exhibit increased ERK, p38 and p70S6 kinase activity. By mixed leukocyte reaction, C1q-DCs show reduced Th1 and Th17 induction from allogeneic CD4(+) T cells. LPS and IFNγ, which cause normal DCs to induce increased CD25 expression on CD4(+) T cells, attenuate C1q-DC induction of CD25. These imply that the DC pericellular C1q may induce tolerogenic properties in developing DCs.
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Blk MD4, 5 Science Drive 2, Singapore 117597, Singapore.
authors.forename: Boon King
authors.initials: BK
authors.lastname: Teh
authors.forename: Joo Guan
authors.initials: JG
authors.lastname: Yeo
authors.forename: Lai Min
authors.initials: LM
authors.lastname: Chern
authors.forename: Jinhua
authors.initials: J
authors.lastname: Lu
mesh_terms: D017209:Apoptosis; D015922:Complement C1q / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000166:cytology* / Q000201:enzymology / Q000276:immunology*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D053759:Interleukin-23 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D009000:Monocytes / Q000166:cytology*; D010587:Phagocytosis; D010641:Phenotype; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D053759:Interleukin-23; D016753:Interleukin-10; D018664:Interleukin-12; D015922:Complement C1q; D007371:Interferon-gamma; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases