Integrin alpha E(CD103)beta 7 influences cellular shape and motility
in a ligand-dependent fashion
Blood, 112 (3):
619-25 (August 2008)Schlickum, Stephanie Sennefelder, Helga Friedrich, Mike Harms, Gregory
Lohse, Martin J Kilshaw, Peter Schon, Michael P Research Support,
Non-U.S. Gov't United States Blood Blood. 2008 Aug 1;112(3):619-25.
Epub 2008 May 20..Abstract
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 alpha(E)(CD103)beta(7) has previously been implicated
in epithelial retention of some T cells through binding to E-cadherin.
Our current data suggest that alpha(E)(CD103)beta(7) also determines
shape and motility of some lymphocytes. Time-lapse microscopy showed
that wild-type alpha(E)(CD103)beta(7) conferred the ability to form
cell protrusions/filopodia and to move in an amoeboid fashion on
E-cadherin, an activity that was abrogated by alpha(E)(CD103)beta(7)-directed
antibodies or cytochalasin D. The alpha(E)-dependent motility was
further increased (P < .001) when point-mutated alpha(E)(CD103) locked
in a constitutively active conformation was expressed. Moreover,
different yellow fluorescent protein-coupled alpha(E)(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 alpha(E)(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 alpha(E)(CD103)-deficient mice (P < .001). Thus, integrin alpha(E)(CD103)beta(7)
is not only involved in epithelial retention, but also in shaping
and proper intraepithelial morphogenesis of some leukocytes.