Interference with islet-specific homing of autoreactive T cells: an emerging therapeutic strategy for type 1 diabetes.
Pathogenesis of type 1 diabetes involves the activation of autoimmune T cells, consequent homing of activated lymphocytes to the pancreatic islets and ensuing destruction of insulin-producing b cells. Interaction between activated lymphocytes and endothelial cells in the islets is the hallmark of the homing process. Initial adhesion, firm adhesion and diapedesis of lymphocytes are the three crucial steps involved in the homing process. Cell-surface receptors including integrins, selectins and hyaluronate receptor CD44 mediate the initial steps of homing. Diapedesis relies on a series of proteolytic events mediated by matrix metalloproteinases. Here, molecular mechanisms governing transendothelial migration of the diabetogenic effector cells are discussed and resulting pharmacological strategies are considered.
Savinov
Alexei Y
AY
Sanford Research/USD, Department of Pediatrics, Sanford School of Medicine of The University of South Dakota, Sioux Falls, SD 57104, USA. asavinov@sanfordhealth.org
Burn
Paul
P
D000818:Animals; D015551:Autoimmunity / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000503:physiopathology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects*
D007004:Hypoglycemic Agents