| First Author | Schmaler M | Year | 2015 |
| Journal | Proc Natl Acad Sci U S A | Volume | 112 |
| Issue | 43 | Pages | 13330-5 |
| PubMed ID | 26450881 | Mgi Jnum | J:227194 |
| Mgi Id | MGI:5699907 | Doi | 10.1073/pnas.1510045112 |
| Citation | Schmaler M, et al. (2015) IL-7R signaling in regulatory T cells maintains peripheral and allograft tolerance in mice. Proc Natl Acad Sci U S A 112(43):13330-5 |
| abstractText | Foxp3(+)CD4(+) regulatory T cells (Treg) have a crucial role in controlling CD4(+) T-cell activation, proliferation, and effector function. However, the molecular mechanisms regulating Treg function remain poorly understood. Here we assessed the role of IL-7, a key cytokine regulating T-cell homeostasis, in suppressor capacity of Treg. Using a skin allograft model in which transplant acceptance is controlled by the number of transferred Treg, we find that Treg impair the proliferation of allogeneic CD4(+) T cells, decrease production of IFNgamma by effector T cells, and prevent early and increase late IL-7 induction by lymph node stromal cells. Increased IL-7 availability enhanced Treg survival, stabilized Treg molecular signature, enhanced surface IL-2Ralpha expression, and improved IL-2 binding of Treg, which diminished proliferation of alloreactive CD4(+) T cells. Sequestration of IL-7 or impairment of IL-7R signaling after allograft transplantation abolished Treg-mediated tolerance by limiting their suppressive capacity. Aged Il7ralpha-DeltaTreg mice displayed mild symptoms of autoimmunity correlating with impaired expansion of effector Treg in response to IL-2. Thus, IL-7R signaling on Treg supports the functional activity of effector Treg by increasing their IL-2 sensitivity in the lymph node during peripheral and allograft tolerance. |
