title: Role for E-cadherin as an inhibitory receptor on epidermal gammadelta T cells.
abstract: E-cadherin is a homophilic adhesion molecule that maintains homotypic intercellular adhesion between epithelial cells such as epidermal keratinocytes. E-cadherin is also expressed on resident murine epidermal γδ T cells, known as dendritic epidermal T cells (DETCs), but they express another receptor for E-cadherin, α(E)(CD103)β(7) integrin, as well. In this study, we analyzed functional differences between E-cadherin-mediated homophilic binding and heterophilic binding of α(E)β(7) integrin to E-cadherin in heterotypic intercellular adhesion of DETCs to keratinocytes. E-cadherin, but not α(E)β(7) integrin, was downregulated on activation of DETCs in vivo and in vitro. Short-term (1-h) adhesion of DETCs to keratinocytes in vitro was primarily mediated by α(E)β(7) integrin, and blocking of the binding of α(E)β(7) integrin to E-cadherin inhibited the lysis of keratinocytes by DETCs. Stable binding of E-cadherin on DETCs to plate-bound recombinant E-cadherin was observed only after 24-h culture in vitro. Cytokine production and degranulation by DETCs in response to suboptimal TCR cross-linking and mitogen stimulation were augmented by coligation of α(E)β(7) integrin. In contrast, engagement of E-cadherin on DETCs with immobilized anti-E-cadherin Ab, plate-bound recombinant E-cadherin, and E-cadherin on keratinocytes inhibited DETC activation. Therefore, E-cadherin acts as an inhibitory receptor on DETCs, whereas α(E)β(7) integrin acts as a costimulatory receptor. Differential expression of E-cadherin and α(E)β(7) integrin on resting and activated DETCs, as well as their opposite functions in DETC activation, suggests that E-cadherin and α(E)β(7) integrin on DETCs regulate their activation threshold through binding to E-cadherin on keratinocytes.
authors.affiliation: Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan.
authors.forename: Youhei
authors.initials: Y
authors.lastname: Uchida
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kawai
authors.forename: Atsuko
authors.initials: A
authors.lastname: Ibusuki
authors.forename: Takuro
authors.initials: T
authors.lastname: Kanekura
mesh_terms: D000818:Animals; D015820:Cadherins / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology; D016023:Integrins / Q000378:metabolism*; D015603:Keratinocytes / Q000276:immunology; D051379:Mice; D011485:Protein Binding; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015820:Cadherins; D016023:Integrins; D016692:Receptors, Antigen, T-Cell, gamma-delta; C070709:integrin alphaEbeta7