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 language | English |
|---|---|
| Pages (from-to) | 1014-1021 |
| Number of pages | 8 |
| Journal | Journal of Immunology |
| Volume | 175 |
| Issue number | 2 |
| Publication status | Published - 2005 Jul 15 |
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ASJC Scopus subject areas
- Immunology
Cite this
Critical role of the fifth domain of E-cadherin for heterophilic adhesion with αEβ7, but not for homophilic adhesion. / Shiraishi, Kiyono; Tsuzaka, Kensei; Yoshimoto, Keiko; Kumazawa, Chika; Nozaki, Kyoko; Abe, Tohru; Tsubota, Kazuo; Takeuchi, Tsutomu.
In: Journal of Immunology, Vol. 175, No. 2, 15.07.2005, p. 1014-1021.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Critical role of the fifth domain of E-cadherin for heterophilic adhesion with αEβ7, but not for homophilic adhesion
AU - Shiraishi, Kiyono
AU - Tsuzaka, Kensei
AU - Yoshimoto, Keiko
AU - Kumazawa, Chika
AU - Nozaki, Kyoko
AU - Abe, Tohru
AU - Tsubota, Kazuo
AU - Takeuchi, Tsutomu
PY - 2005/7/15
Y1 - 2005/7/15
N2 - 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.
AB - 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.
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M3 - Article
VL - 175
SP - 1014
EP - 1021
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 2
ER -