| First Author | Lee JK | Year | 2021 |
| Journal | Cell Mol Immunol | Volume | 18 |
| Issue | 6 | Pages | 1395-1411 |
| PubMed ID | 33850312 | Mgi Jnum | J:322352 |
| Mgi Id | MGI:7258197 | Doi | 10.1038/s41423-021-00671-2 |
| Citation | Lee JK, et al. (2021) Ssu72 is a T-cell receptor-responsive modifier that is indispensable for regulatory T cells. Cell Mol Immunol 18(6):1395-1411 |
| abstractText | The homeostatic balance between effector T cells and regulatory T cells (Tregs) is crucial for adaptive immunity; however, epigenetic programs that inhibit phosphorylation to regulate Treg development, peripheral expression, and suppressive activity are elusive. Here, we found that the Ssu72 phosphatase is activated by various T-cell receptor signaling pathways, including the T-cell receptor and IL-2R pathways, and localizes at the cell membrane. Deletion of Ssu72 in T cells disrupts CD4(+) T-cell differentiation into Tregs in the periphery via the production of high levels of the effector cytokines IL-2 and IFNgamma, which induce CD4(+) T-cell activation and differentiation into effector cell lineages. We also found a close correlation between downregulation of Ssu72 and severe defects in mucosal tolerance in patients. Interestingly, Ssu72 forms a complex with PLCgamma1, which is an essential effector molecule for T-cell receptor signaling as well as Treg development and function. Ssu72 deficiency impairs PLCgamma1 downstream signaling and results in failure of Foxp3 induction. Thus, our studies show that the Ssu72-mediated cytokine response coordinates the differentiation and function of Treg cells in the periphery. |
