Regulation of NK cell trafficking by CD81.
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.
Krämer
Benjamin
B
Department of Internal Medicine I, University of Bonn, Bonn, Germany.
Schulte
Daniela
D
Körner
Christian
C
Zwank
Claudia
C
Hartmann
Agathe
A
Michalk
Monika
M
Söhne
Jennifer
J
Langhans
Bettina
B
Nischalke
Hans-Dieter
HD
Coenen
Martin
M
Möhl
Christoph
C
Vogt
Annabelle
A
Hennenberg
Martin
M
Sauerbruch
Tilman
T
Spengler
Ulrich
U
Nattermann
Jacob
J
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
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