MafB is a critical regulator of complement component C1q

Nat Commun. 2017 Nov 22;8(1):1700. doi: 10.1038/s41467-017-01711-0.

Abstract

The transcription factor MafB is expressed by monocytes and macrophages. Efferocytosis (apoptotic cell uptake) by macrophages is important for inhibiting the development of autoimmune diseases, and is greatly reduced in Mafb-deficient macrophages. Here, we show the expression of the first protein in the classical complement pathway C1q is important for mediating efferocytosis and is reduced in Mafb-deficient macrophages. The efferocytosis defect in Mafb-deficient macrophages can be rescued by adding serum from wild-type mice, but not by adding serum from C1q-deficient mice. By hemolysis assay we also show that activation of the classical complement pathway is decreased in Mafb-deficient mice. In addition, MafB overexpression induces C1q-dependent gene expression and signals that induce C1q genes are less effective in the absence of MafB. We also show that Mafb-deficiency can increase glomerular autoimmunity, including anti-nuclear antibody deposition. These results show that MafB is an important regulator of C1q.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Autoimmunity
  • Complement C1q / deficiency
  • Complement C1q / genetics
  • Complement C1q / metabolism*
  • Complement Pathway, Classical
  • Gene Expression Regulation
  • Gene Knockout Techniques
  • Humans
  • Macrophages / cytology
  • Macrophages / immunology
  • Macrophages / metabolism
  • MafB Transcription Factor / deficiency
  • MafB Transcription Factor / genetics
  • MafB Transcription Factor / immunology*
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / immunology
  • RAW 264.7 Cells
  • Zebrafish / genetics
  • Zebrafish Proteins / deficiency
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / immunology

Substances

  • MAFB protein, human
  • MafB Transcription Factor
  • Mafb protein, mouse
  • Nerve Tissue Proteins
  • Zebrafish Proteins
  • mafb protein, zebrafish
  • Complement C1q