4.5 Article

Expression of complement components, receptors and regulators by human dendritic cells

Journal

MOLECULAR IMMUNOLOGY
Volume 48, Issue 9-10, Pages 1121-1127

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2011.02.003

Keywords

Complement; Dendritic cell; Local production; Gene regulation

Funding

  1. Medical Research Council of the UK
  2. Department of Health via the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre
  3. King's College London
  4. King's College Hospital NHS Foundation Trust
  5. Medical Research Council [G0600892, G0600698B, G0601202] Funding Source: researchfish
  6. MRC [G0600892, G0601202] Funding Source: UKRI

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Integration of innate and adaptive arms of the immune response at a cellular and molecular level appears to be fundamental to the development of powerful effector functions in host defence and aberrant immune responses. Here we provide evidence that the functions of human complement activation and antigen presentation converge on dendritic cells (DCs). We show that several subsets of human DCs [i.e., monocyte derived (CD1a(+)CD14(-)), dermal (CD1a(+)DC-SIGN(+)), Langerhans (CD1a(+)Langerin(+)), myeloid (CD1c(+)CD19(-)), plamacytoid (CD45RA(+)CD123(+))] express many of the components of the classical and alternative and terminal pathways of complement. Moreover human DCs have receptors known to detect the biologically active peptides C3a and C5a (C3aR, C5aR) and the covalently bound fragments C3b and metabolites iC3b and C3d which serve in immune adhesion (i.e., CR3, CR4, CRIg). We also show that the human DC surface is characterised by membrane bound regulators of complement activation, which are also known to participate in intracellular signalling (i.e., CD46, CD55, CD59). This work provides an extensive description of complement components relevant to the integrated actions of complement and DC, illuminated by animal studies. It acts as a resource that allows further understanding and exploitation of role of complement in human health and immune mediated diseases. (C) 2011 Elsevier Ltd. All rights reserved.

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