title: Regulation of NK cell trafficking by CD81.
abstract: NK cells, a heterogeneous sub-population of lymphocytes, are critically involved in the regulation of both innate and adaptive immune responses in humans. Besides their participation in the control of tumors and viral infections, they also regulate inflammatory processes, mediating both beneficial and detrimental effects. To effectively fulfil their role in immune surveillance, proper trafficking of NK cells is essential. However, the mechanisms and factors governing NK cell recruitment are only poorly dissected. Here, we describe the functional role of tetraspanins, a family of evolutionary conserved cell-surface proteins, in modulating migration and transmigration of human NK cells. We demonstrate expression of various tetraspanins on NK cells. Furthermore, we show that stimulation of the NK cell-expressed tetraspanin CD81 induces phosphorylation of ezrin/radixin/moesin proteins and leads to NK cell polarization thereby facilitating NK cell migration toward various chemokines/cytokines. Finally, we provide evidence for a role of CD81 in promoting adhesion of NK cells to components of the extracellular matrix, a prerequisite for extravasation of lymphocytes in inflamed tissues. Thus, our data suggest that the tetraspanin CD81 is importantly involved in the regulation of NK cell recruitment.
authors.affiliation: Department of Internal Medicine I, University of Bonn, Bonn, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Krämer
authors.forename: Daniela
authors.initials: D
authors.lastname: Schulte
authors.forename: Christian
authors.initials: C
authors.lastname: Körner
authors.forename: Claudia
authors.initials: C
authors.lastname: Zwank
authors.forename: Agathe
authors.initials: A
authors.lastname: Hartmann
authors.forename: Monika
authors.initials: M
authors.lastname: Michalk
authors.forename: Jennifer
authors.initials: J
authors.lastname: Söhne
authors.forename: Bettina
authors.initials: B
authors.lastname: Langhans
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Nischalke
authors.forename: Martin
authors.initials: M
authors.lastname: Coenen
authors.forename: Christoph
authors.initials: C
authors.lastname: Möhl
authors.forename: Annabelle
authors.initials: A
authors.lastname: Vogt
authors.forename: Martin
authors.initials: M
authors.lastname: Hennenberg
authors.forename: Tilman
authors.initials: T
authors.lastname: Sauerbruch
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
authors.forename: Jacob
authors.initials: J
authors.lastname: Nattermann
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D016764:Cell Polarity; D018946:Chemokine CCL5 / Q000378:metabolism / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D010766:Phosphorylation; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D060225:Tetraspanin 28; D060149:Tetraspanin 30; D054460:rho-Associated Kinases / Q000378:metabolism; D000099149:Ezrin
chemical_list: D015703:Antigens, CD; D018946:Chemokine CCL5; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D010980:Platelet Membrane Glycoproteins; D011493:Protein Kinase C; D060225:Tetraspanin 28; D060149:Tetraspanin 30; D054460:rho-Associated Kinases; D000099149:Ezrin; C554586:CD63 protein, human; C554798:CD81 protein, human; C071058:moesin; C071776:radixin