Complement C1q regulates LPS-induced cytokine production in bone marrow-derived dendritic cells

Eur J Immunol. 2004 Jan;34(1):221-30. doi: 10.1002/eji.200324026.


We show here that C1q suppresses IL-12p40 production in LPS-stimulated murine bone marrow-derived dendritic cells (BMDC). Serum IL-12p40 concentration of C1q-deficient mice was higher than that of wild-type mice after intraperitoneal LPS-injection. Because neither globular head of C1q (gC1q) nor collagen-like region of C1q (cC1q) failed to suppress LPS-induced IL-12p40 production, both gC1q and cC1q, and/or some specialized conformation of native C1q may be required for the inhibition. While C1q did not affect mRNA expression of Toll-like receptor 4 (TLR4), MD-2, and myeloid differentiation factor 88 (MyD88), BMDC treated with C1q showed the reduced activity of NF-kappaB and the delayed phosphorylation of p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase after LPS-stimulation. CpG oligodeoxynucleotide-induced IL-12p40 and TNF-alpha production, another MyD88-dependent TLR-mediated signal, was also suppressed by C1q treatment. Therefore, C1q is likely to suppress MyD88-dependent pathway in TLR-mediated signals. In contrast, C1q failed to suppress colony formation of B cells responding to LPS or LPS-induced CD40 and CD86 expression on BMDC in MyD88-deficient mice, indicating that inhibitory effects of C1q on MyD88-independent pathways may be limited. Taken together, C1q may regulate innate and adaptive immune systems via modification of signals mediated by interactions between invading pathogens and TLR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / metabolism
  • Antigens, Ly / genetics
  • Antigens, Ly / metabolism
  • Bone Marrow Cells / metabolism*
  • Complement C1q / metabolism*
  • Cytokines / biosynthesis*
  • Dendritic Cells / metabolism*
  • Female
  • Interleukin-12 / biosynthesis
  • Interleukin-12 Subunit p40
  • Lipopolysaccharides / metabolism
  • Lymphocyte Antigen 96
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Myeloid Differentiation Factor 88
  • Protein Subunits / biosynthesis
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism
  • Signal Transduction / physiology
  • Toll-Like Receptor 4
  • Toll-Like Receptors


  • Adaptor Proteins, Signal Transducing
  • Antigens, Differentiation
  • Antigens, Ly
  • Cytokines
  • Interleukin-12 Subunit p40
  • Lipopolysaccharides
  • Ly96 protein, mouse
  • Lymphocyte Antigen 96
  • Membrane Glycoproteins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Protein Subunits
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Interleukin-12
  • Complement C1q