| First Author | Schäll D | Year | 2015 |
| Journal | Eur J Immunol | Volume | 45 |
| Issue | 11 | Pages | 3087-97 |
| PubMed ID | 26306874 | Mgi Jnum | J:233656 |
| Mgi Id | MGI:5787756 | Doi | 10.1002/eji.201545609 |
| Citation | Schall D, et al. (2015) SLy1 regulates T-cell proliferation during Listeria monocytogenes infection in a Foxo1-dependent manner. Eur J Immunol 45(11):3087-97 |
| abstractText | Infection of mice with Listeria monocytogenes results in a strong T-cell response that is critical for an efficient defense. Here, we demonstrate that the adapter protein SLy1 (SH3-domain protein expressed in Lymphocytes 1) is essential for the generation of a fully functional T-cell response. The lack of SLy1 leads to reduced survival rates of infected mice. The increased susceptibility of SLy1 knock-out (KO) mice was caused by reduced proliferation of differentiated T cells. Ex vivo analyses of isolated SLy1 KO T cells displayed a dysregulation of Forkhead box protein O1 shuttling after TCR signaling, which resulted in an increased expression of cell cycle inhibiting genes, and therefore, reduced expansion of the T-cell population. Forkhead box protein O1 shuttles to the cytoplasm after phosphorylation in a protein complex including 14-3-3 proteins. Interestingly, we observed a similar regulation for the adapter protein SLy1, where TCR stimulation results in SLy1 phosphorylation and SLy1 export to the cytoplasm. Moreover, immunoprecipitation analyses revealed a binding of SLy1 to 14-3-3 proteins. Altogether, this study describes SLy1 as an immunoregulatory protein, which is involved in the generation of adaptive immune responses during L. monocytogenes infection, and provides a model of how SLy1 regulates T-cell proliferation. |
