Critical role of the fifth domain of E-cadherin for heterophilic adhesion with αEβ7, but not for homophilic adhesion

Kiyono Shiraishi, Kensei Tsuzaka, Keiko Yoshimoto, Chika Kumazawa, Kyoko Nozaki, Tohru Abe, Kazuo Tsubota, Tsutomu Takeuchi

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The integrin αEβ7 is expressed on intestinal intraepithelial T lymphocytes and CD8+ T lymphocytes in inflammatory lesions near epithelial cells. Adhesion between αEβ7+ T and epithelial cells is mediated by the adhesive interaction of αEβ7 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 αEβ 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 αEβ7+ K562 cells were incubated with L cells expressing the wild type, 23% of the resulting cell aggregates consisted of αEβ7+ K562 cells. In contrast, the binding of αEβ7+ K562 cells to L cells expressing a domain 5-deficient mutant was significantly decreased, with αEβ7+ 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 αEβ7, 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 αEβ7 and may be a potential target for treatments altering the adhesion of αEβ7 + T cells to epithelial cells in inflammatory epithelial diseases.

Original languageEnglish
Pages (from-to)1014-1021
Number of pages8
JournalJournal of Immunology
Volume175
Issue number2
DOIs
Publication statusPublished - 2005 Jul 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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