Details

Autor(en) / Beteiligte

• Serrano‐Pertierra, Esther
• Cernuda‐Morollón, Eva
• López‐Larrea, Carlos

Titel

Wiskott‐Aldrich syndrome protein (WASp) and N‐WASp are involved in the regulation of NK‐cell migration upon NKG2D activation

Ist Teil von

• European journal of immunology, 2012-08, Vol.42 (8), p.2142-2151

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2012

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• NKG2D is a transmembrane receptor mainly expressed on CD8+ T cells and NK cells. Engagement of NKG2D with its ligands can trigger a cytotoxic response. It has been shown that tumor cells deliver soluble NKG2D ligands as a mechanism of immune evasion through the downregulation of surface‐expressed NKG2D. These ligands may be also secreted in microvesicles and regulate NK‐cell function, but the existence of alternative mechanisms has not been explored. In this study, we describe that NKG2D activation inhibits NK‐cell chemotaxis toward a CXCL12 gradient. Costimulation of the inhibitory receptor NKG2A rescues NK‐cell migration rates. Thus, the balance of NKG2D/NKG2A activation may determine the migratory ability of NK cells. Furthermore, our data indicated that NKG2D cross‐linking induces the activation of the Rho GTPases Rac1 and Cdc42, while RhoA activity is decreased. Pharmacological inhibition of the Cdc42 effectors Wiskott‐Aldrich syndrome protein (WASp)/N‐WASp, and the reduction of their levels using RNA interference partially abolished NKG2D‐mediated impairment of cell migration, suggesting a pivotal role of Cdc42 in the regulation of NK‐cell migration by NKG2D activation. Therefore, our results provide a new mechanism that may contribute to the immune response or evasion in tumors.