| First Author | Mercadante ER | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 1 | Pages | 129-137 |
| PubMed ID | 28550200 | Mgi Jnum | J:251015 |
| Mgi Id | MGI:6099583 | Doi | 10.4049/jimmunol.1602171 |
| Citation | Mercadante ER, et al. (2017) T Cells Deficient in the Tyrosine Phosphatase SHP-1 Resist Suppression by Regulatory T Cells. J Immunol 199(1):129-137 |
| abstractText | The balance between activation of T cells and their suppression by regulatory T cells (Tregs) is dysregulated in autoimmune diseases and cancer. Autoimmune diseases feature T cells that are resistant to suppression by Tregs, whereas in cancer, T cells are unable to mount antitumor responses due to the Treg-enriched suppressive microenvironment. In this study, we observed that loss of the tyrosine phosphatase SHP-1, a negative regulator of TCR signaling, renders naive CD4(+) and CD8(+) T cells resistant to Treg-mediated suppression in a T cell-intrinsic manner. At the intracellular level, SHP-1 controlled the extent of Akt activation, which has been linked to the induction of T cell resistance to Treg suppression. Finally, under conditions of homeostatic expansion, SHP-1-deficient CD4(+) T cells resisted Treg suppression in vivo. Collectively, these data establish SHP-1 as a critical player in setting the threshold downstream of TCR signaling and identify a novel function of SHP-1 as a regulator of T cell susceptibility to Treg-mediated suppression in vitro and in vivo. Thus, SHP-1 could represent a potential novel immunotherapeutic target to modulate susceptibility of T cells to Treg suppression. |
