The alpha E(CD103)beta 7 integrin interacts with oral and skin keratinocytes in an E-cadherin-independent manner

作者：Jenkinson Sarah E; Whawell Simon A; Swales Brenka M; Corps Elaine M; Kilshaw Peter J; Farthing Paula M^*

来源：Immunology, 2011, 132(2): 188-196.

DOI：10.1111/j.1365-2567.2010.03352.x

• adhesion
• integrin
• keratinocytes
• mucosal immunology
• T cells

P>The integrin alpha E(CD103)beta 7 (alpha E beta 7) is expressed by intraepithelial lymphocytes, dendritic cells and regulatory T cells. It plays an important role in the mucosal immune system by retaining lymphocytes within the epithelium and is involved in graft rejection, immunity against tumours and the generation of gut-homing effector cells. In gut and breast, the ligand for alpha E beta 7 is E-cadherin but in human oral mucosa and skin, there is evidence that lymphocytes use an alternative, unknown, ligand. In the present study, the I domain of the human alpha E subunit, which contains the E-cadherin-binding site, was locked in a highly active, 'open' and an inactive, 'closed' conformation by the introduction of disulphide bonds and these domains were expressed as IgG Fc fusion proteins. alpha E fusion proteins recognize E-cadherin, the only known ligand for alpha E beta 7. This interaction was inhibited by an antibody that blocks the alpha E-binding site on E-cadherin and by the omission of Mn(2+), which is essential for integrin function in vitro. The locked 'open' conformation of alpha E adhered to human oral and skin keratinocytes, including the E-cadherin-negative H376 cell line, and this was not inhibited by blocking antibody against the alpha E beta 7-binding site on E-cadherin, providing further evidence for the existence of an alternative ligand for alpha E beta 7 in skin and oral mucosa. The interaction with E-cadherin and the alternative ligand was Mn(2+) dependent and mediated by the metal ion-dependent coordination site (MIDAS) of the locked 'open'alpha E I domain, independently of the beta 7 subunit.

• 出版日期2011-2