CD46: the 'multitasker' of complement proteins

Abstract

Complement is undeniably quintessential for innate immunity by detecting and eliminating infectious microorganisms. Recent work, however, highlights an equally profound impact of complement on the induction and regulation of a wide range of immune cells. In particular, the complement regulator CD46 emerges as a key sensor of immune activation and a vital modulator of adaptive immunity. In this review, we summarize the current knowledge of CD46-mediated signalling events and their functional consequences on immune-competent cells with a specific focus on those in CD4(+) T cells. We will also discuss the promises and challenges that potential therapeutic modulation of CD46 may hold and pose.

Keywords: (CBF1/Su(H)/Lag-1) transcription factor complex; ADAM; AMD; AP-1; Autoimmunity; B-cell lymphoma 2; Bcl-2; CCL; CCP; CD46; CD46 cytoplasmic domain 1 or 2; CSL; CYT-1 or CYT-2; Complement; DC; DLG4; DLL; ERK1/2; FLT3; FLT3L; FMS-related tyrosine kinase 3; FMS-related tyrosine kinase 3 ligand; G protein-coupled receptor; G protein-coupled receptor kinase; GAS; GATA3; GOPC; GPCR; GRK; GSK3β; GTP; Group A Streptococcus pyogenes; ICER/CREM; IFN; IL; IPEX; IS; Infection; JAK; JNK; Janus kinase; LAT; LDL receptor-related protein; LEF; LRP; Lck; MAPK; MHC; MMP; MS; MTOC; NF-κB; NICD; NO; Notch intracellular domain; PGE2; RA; RCA; SLE; SNP; SP-1; SPAK; STAT; STP region; Ste20/SPS-1-related kinase; T cell receptor; T helper cell/response; T-bet; T-box transcription factor TBX21; T-cell factor/lymphocyte-enhancer-binding factor; TCR; TER; TLR; Th; Th1 cells; Toll-like receptor; UT; a disintegrin and metalloproteinase; aHUS; activator protein 1; age-related macular degeneration; atypical hemolytic uremic syndrome; c-Jun amino-terminal kinase; chemokine (C-C motif) ligand; complement control protein domain; delta-like ligand; dendritic cell; extracellular signal-regulated protein kinases 1 and 2; glycogen synthase kinase 3β; golgi-associated PDZ and coiled-coil motif-containing protein; guanine triphosphate; human homologue of Discs Large (DLG) Drosophila; immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like; immunological synapse; inducible cAMP early repressor/cAMP response element modulator; interferon; interleukin; linker for activation of T cells; lymphocyte-specific protein tyrosine kinase; major histocompatibility complex; matrix metalloproteinase; microtubule organizing centre; mitogen-activated protein kinase; multiple sclerosis; nTreg; natural regulatory T cell; nitric oxide; nuclear factor kappa-light-chain-enhancer of activated B cells; prostaglandin E2; regulators of complement activity; rheumatoid arthritis; serine, threonine, proline-rich region; signal transducer and activator of transcription; single-nucleotide polymorphism; specificity protein 1; systemic lupus erythematosus; trans-acting T-cell-specific transcription factor GATA3; transepithelial resistance; untranslated region.