The role of cell adhesion molecules in the development of IDDM: implications for pathogenesis and therapy.
IDDM is a chronic inflammatory disease in which there is autoimmune-mediated organ-specific destruction of the insulin-producing beta-cells in the pancreatic islets of Langerhans. The migration of autoreactive lymphocytes and other leukocytes from the bloodstream into the target organ is of clear importance in the etiology of many organ-specific autoimmune/inflammatory disorders, including IDDM. In IDDM, this migration results in lymphocytic invasion of the islets (formation of insulitis) and subsequent destruction of beta-cells. Migration of lymphocytes from the bloodstream into tissues is a complex process involving sequential adhesion and activation events. This migration is controlled in part by selective expression and functional regulation of cell adhesion molecules (CAMs) on the surface of lymphocytes and vascular endothelial cells or in the extracellular matrix. Understanding the mechanisms that regulate lymphocyte migration to the pancreatic islets will lead to further understanding of the pathogenesis of IDDM. In this article, we summarize the recent advances regarding the function of CAMs in the development of IDDM in animal models and in humans and discuss the potential for developing CAM-based therapies for IDDM.
Yang
X D
XD
Department of Immunology, Cell Genesys, Foster City, CA 94404, USA.
Michie
S A
SA
Mebius
R E
RE
Tisch
R
R
Weissman
I
I
McDevitt
H O
HO
D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D008954:Models, Biological
D015815:Cell Adhesion Molecules