Integrin αE(CD103)β7 influences cellular shape and motility in a ligand-dependent fashion

While the extravasation cascade of lymphocytes is well characterized, data on their intraepithelial positioning and morphology are scant. However, the latter process is presumably crucial for many immune functions. Integrin aE(CD103)[37 has previously been implicated in epithelial retention of some T cells through binding to E-cadherin. Our current data suggest that aE(CD103)(37 also determines shape and motility of some lymphocytes. Time-lapse microscopy showed that wild-type aE(CD103)(37 conferred the ability to form cell protrusions/filopodia and to move in an amoeboid fashion on E-cadherin, an activity that was abrogated by aE(CD103)(3z-directed antibodies or cytochalasin D. The aE-dependent motility was further increased (P <.001) when point-mutated aE(CD103) locked in a constitutively active conformation was expressed. Moreover, different yellow fluorescent protein-coupled aE(CD103) species demonstrated that the number and length of filopodia extended toward purified E-cadherin, cocultured keratinocytes, cryostat-cut skin sections, or epidermal sheets depended on functional aE(CD103). The in vivo relevance of these findings was demonstrated by wild-type dendritic epidermal T cells (DETCs), which showed significantly more dendrites and spanned larger epidermal areas as compared with DETCs of aE(CD103)-deficient mice (P <.001). Thus, integrin aE(CD103)[37 is not only involved in epithelial retention, but also in shaping and proper intraepithelial morphogenesis of some leukocytes.