| First Author | Garçon F | Year | 2016 |
| Journal | Immunol Cell Biol | Volume | 94 |
| Issue | 5 | Pages | 486-95 |
| PubMed ID | 26740009 | Mgi Jnum | J:339385 |
| Mgi Id | MGI:6869145 | Doi | 10.1038/icb.2016.1 |
| Citation | Garcon F, et al. (2016) PI3Kdelta promotes CD4(+) T-cell interactions with antigen-presenting cells by increasing LFA-1 binding to ICAM-1. Immunol Cell Biol 94(5):486-95 |
| abstractText | Activation of T lymphocytes by peptide/major histocompatibility complex on antigen-presenting cells (APCs) involves dynamic contacts between the two cells, during which T cells undergo marked morphological changes. These interactions are facilitated by integrins. Activation of the T cells increases the binding of the integrin lymphocyte function-associated antigen 1 (LFA-1) expressed by T cells to intercellular adhesion molecule (ICAM)-1 and ICAM-2 expressed by APCs. The signalling pathways that control integrin affinities are incompletely defined. The phosphoinositide 3-kinases (PI3Ks) generate second-messenger signalling molecules that control cell growth, proliferation, differentiation and trafficking. Here we show that in T cells, PI3Kdelta attenuates the activation of Rac1, but sustains the activation of Rap1. Consequently, PI3Kdelta increases LFA-1-dependent adhesion to form stable conjugates with APCs. Increased Rap1 activity and LFA-1 adhesion were only in part mediated by the downstream kinase Akt, suggesting the involvement of additional phosphatidylinositol(3,4,5)P3-binding proteins. These results establish a link between PI3K activity, cytoskeletal changes and integrin binding and help explain the impaired T-cell-dependent immune responses in PI3Kdelta-deficient mice. |
