Critical role of the fifth domain of E-cadherin for heterophilic adhesion with αEβ 7 but not for homophilic adhesion
Critical role of the fifth domain of E-cadherin for heterophilic adhesion with αEβ 7 but not for homophilic adhesion
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DOI：
10.4049/jimmunol.175.2.1014
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发表时间：
2005-07-15
影响因子：
4.4
通讯作者：
Takeuchi, T
中科院分区：
文献类型：
--
作者：
Shiraishi, K;Tsuzaka, K;Takeuchi, T
The integrin alpha(E)beta(7) is expressed on intestinal intraepithelial T lymphocytes and CD8(+) T lymphocytes in inflammatory lesions near epithelial cells. Adhesion between a,alpha(E)beta(+)(7) T and epithelial cells is mediated by the adhesive interaction of alpha(E)beta(7) and E-cadherin; this interaction plays a key role in the damage of target epithelia. To explore the structure-function relationship of the heterophilic adhesive interaction between E-cadherin and alpha(E)beta(7), we performed cell aggregation assays using L cells transfected with an extracellular domain-deletion mutant of E-cadherin. In homophilic adhesion assays, L cells transfected with wild-type or a domain 5-deficient mutant formed aggregates, whereas transfectants with domain 1-, 2-, 3-, or 4-deficient mutants did not. These results indicate that not only domain 1, but domains 2, 3, and 4 are involved in homophilic adhesion. When alpha(E)beta(+)(7) K562 cells were incubated with L cells expressing the-wild type, 23% of the resulting cell aggregates consisted of alpha(E)beta(+)(7) K562 cells. In contrast, the binding of alpha(E)beta(+)(7) K562 cells to L cells expressing a domain 5-deficient mutant was significantly decreased, with alpha(E)beta(+)(7) K562 cells accounting for only 4% of the cell aggregates, while homophilic adhesion was completely preserved. These results suggest that domain 5 is involved in heterophilic adhesion with alpha(E)beta(7), but not in homophilic adhesion, leading to the hypothesis that the fifth domain of E-cadherin may play a critical role in the regulation of heterophilic adhesion to alpha(E)beta(7) and may be a potential target for treatments altering the adhesion of alpha(E)beta(+)(7) T cells to epithelial cells in inflammatory epithelial diseases.
