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
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
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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U2 - 10.4049/jimmunol.175.2.1014
DO - 10.4049/jimmunol.175.2.1014
M3 - Article
C2 - 16002701
AN - SCOPUS:23244433057
VL - 175
SP - 1014
EP - 1021
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 2
ER -