| First Author | Borlido J | Year | 2018 |
| Journal | Nat Immunol | Volume | 19 |
| Issue | 6 | Pages | 594-605 |
| PubMed ID | 29736031 | Mgi Jnum | J:282451 |
| Mgi Id | MGI:6380965 | Doi | 10.1038/s41590-018-0103-5 |
| Citation | Borlido J, et al. (2018) Nuclear pore complex-mediated modulation of TCR signaling is required for naive CD4(+) T cell homeostasis. Nat Immunol 19(6):594-605 |
| abstractText | Nuclear pore complexes (NPCs) are channels connecting the nucleus with the cytoplasm. We report that loss of the tissue-specific NPC component Nup210 causes a severe deficit of naive CD4(+) T cells. Nup210-deficient CD4(+) T lymphocytes develop normally but fail to survive in the periphery. The decreased survival results from both an impaired ability to transmit tonic T cell receptor (TCR) signals and increased levels of Fas, which sensitize Nup210(-/-) naive CD4(+) T cells to Fas-mediated cell death. Mechanistically, Nup210 regulates these processes by modulating the expression of Cav2 (encoding Caveolin-2) and Jun at the nuclear periphery. Whereas the TCR-dependent and CD4(+) T cell-specific upregulation of Cav2 is critical for proximal TCR signaling, cJun expression is required for STAT3-dependent repression of Fas. Our results uncover an unexpected role for Nup210 as a cell-intrinsic regulator of TCR signaling and T cell homeostasis and expose NPCs as key players in the adaptive immune system. |
