Endothelial Expression of MHC Class II Molecules in Autoimmune Disease

Author: Turesson, Carl1

Source: Current Pharmaceutical Design, Volume 10, Number 2, January 2004 , pp. 129-143(15)

Publisher: Bentham Science Publishers

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Abstract:

Major histocompatibility complex (MHC) class II molecules are up-regulated on endothelial cells in human allografts, and are thought to be involved in graft rejection. The MHC class II subtypes HLA-DR, DQ and DP regulate T cell dependent immune responses, and aberrant expression could be important in autoimmunity. Increased endothelial MHC class II expression has been demonstrated in several autoimmune diseases, including myocarditis with dilated cardiomyopathy, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Recent data suggest that there is an association between endothelial expression of MHC class II molecules and diffuse endothelial dysfunction, which may be part of the explanation of the increased risk of cardiovascular disease in patients with RA, SLE and other chronic inflammatory conditions. MHC class II transcription is in part genetically determined. Cytokine induced up-regulation of MHC class II molecules can be inhibited in vitro by antioxidants and different drugs, such as cyclosporin and statins. Research on the development of new treatments for systemic autoimmune diseases and cardiovascular disease should include evaluation of effects on endothelial activation, including MHC class II expression.

This review also discusses the genetic basis of MHC class II expression and its implications for understanding MHC genotype associations with autoimmune diseases. Recent studies of interactions between endothelial cells and T cells are reviewed. Such interactions could be of major importance in the pathogenesis of autoimmune and vascular diseases.

Keywords: major histocompatibility complex class II; endothelial cells; endothelial activation; major histocompatibility complex class II

Document Type: Review article

DOI: 10.2174/1381612043453414

Affiliations: 1: Rheumatology Laboratory, 401 Guggenheim, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA..

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