CD46 processing: A means of expression

Ni Choileain S., Astier A. L.

IMMUNOBIOLOGY, vol.217, no.2, pp.169-175, 2012 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 217 Issue: 2
  • Publication Date: 2012
  • Doi Number: 10.1016/j.imbio.2011.06.003
  • Journal Name: IMMUNOBIOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.169-175
  • Keywords: CD46, Enzymatic processing, Gamma-secretase, Matrix metalloproteinases, T cells, MEMBRANE COFACTOR PROTEIN, COMPLEMENT REGULATORY PROTEIN, CD4(+) T-CELLS, CELLULAR PILUS RECEPTOR, MEASLES-VIRUS RECEPTOR, MULTIPLE-SCLEROSIS, DOWN-REGULATION, CYTOPLASMIC DOMAINS, PATHOGEN RECEPTOR, DENDRITIC CELLS
  • Dokuz Eylül University Affiliated: No

Abstract

CD46 is a ubiquitously expressed type I transmembrane protein, first identified as a regulator of complement activation, and later as an entry receptor for a variety of pathogens. The last decade has also revealed the role of CD46 in regulating the adaptive immune response, acting as an additional costimulatory molecule for human T cells and inducing their differentiation into Tr1 cells, a subset of regulatory T cells. Interestingly, CD46 regulatory pathways are defective in T cells from patients with multiple sclerosis, asthma and rheumatoid arthritis, illustrating its importance in regulating T cell homeostasis. Indeed, CD46 expression at the cell surface is tightly regulated in many different cell types, highlighting its importance in several biological processes. Notably, CD46 is the target of enzymatic processing, being cleaved by metalloproteinases and by the presenilin/gamma secretase complex. This processing is required for its functions, at least in T cells. This review will summarize the latest updates on the regulation of CD46 expression and on its effects on T cell activation. (C) 2011 Elsevier GmbH. All rights reserved.