Integrin alpha E(CD103)beta 7 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 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.
Schlickum
Stephanie
S
Rudolf Virchow Center, Deutsche Forschungsgemeinschaft (DFG) Research Center for Experimental Biomedicine, Department of Dermatology, University of Würzburg, Würzburg, Germany.
Sennefelder
Helga
H
Friedrich
Mike
M
Harms
Gregory
G
Lohse
Martin J
MJ
Kilshaw
Peter
P
Schön
Michael P
MP
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement; D048430:Cell Shape; D018920:Coculture Techniques; D000078404:Epidermal Cells; D006801:Humans; D016023:Integrins / Q000502:physiology*; D020014:K562 Cells; D015603:Keratinocytes / Q000166:cytology; D007962:Leukocytes / Q000166:cytology*; D008024:Ligands; D051379:Mice; D011554:Pseudopodia; D013601:T-Lymphocytes / Q000166:cytology
D015820:Cadherins; D016023:Integrins; D008024:Ligands; C070709:integrin alphaEbeta7