| First Author | Wernimont SA | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 8 | Pages | 4714-23 |
| PubMed ID | 20855869 | Mgi Jnum | J:164732 |
| Mgi Id | MGI:4835096 | Doi | 10.4049/jimmunol.1001445 |
| Citation | Wernimont SA, et al. (2010) PIPKI gamma 90 negatively regulates LFA-1-mediated adhesion and activation in antigen-induced CD4+ T cells. J Immunol 185(8):4714-23 |
| abstractText | T cell activation requires the formation and maintenance of stable interactions between T cells and APCs. The formation of stable T cell-APC contacts depends on the activation of the integrin LFA-1 (CD11aCD18). Several positive regulators of LFA-1 activation downstream of proximal TCR signaling have been identified, including talin; however, negative regulators of LFA-1 activity remain largely unexplored. Extended isoform of phosphatidylinositol phosphate kinase type I gamma (PIPKIgamma90) is a member of the type I phosphatidylinositol phosphate kinase family that has been shown previously to modulate talin activation of integrins through production of phosphatidylinositol 4,5-bisphosphate and direct binding to talin. In this study, we show that PIPKIgamma90 negatively regulates LFA-1-mediated adhesion and activation of T cells. Using CD4(+) T cells from PIPKIgamma90-deficient mice, we show that CD4(+) T cells exhibit increased LFA-1-dependent adhesion to ICAM-1 and increased rates of T cell-APC conjugate formation with enhanced LFA-1 polarization at the synapse. In addition to increased adhesiveness, PIPKIgamma90-deficient T cells exhibit increased proliferation both in vitro and in vivo and increased production of IFN-gamma and IL-2. Together, these results demonstrate that PIPKIgamma90 is a negative regulator of Ag-induced T cell adhesion and activation. |
