| First Author | Silva A | Year | 2014 |
| Journal | Proc Natl Acad Sci U S A | Volume | 111 |
| Issue | 9 | Pages | E846-55 |
| PubMed ID | 24550492 | Mgi Jnum | J:207405 |
| Mgi Id | MGI:5556336 | Doi | 10.1073/pnas.1319397111 |
| Citation | Silva A, et al. (2014) NF-kappaB signaling mediates homeostatic maturation of new T cells. Proc Natl Acad Sci U S A 111(9):E846-55 |
| abstractText | Interleukin (IL)-7 is critical for the maintenance of the peripheral T-cell compartment of the adaptive immune system. IL-7 receptor alpha ( IL-7Ralpha) expression is subject to developmental regulation and new T cells induce expression as they leave the thymus, which is essential for their long-term survival. It is not understood how this expression is regulated. Here, we identify a role for the Nuclear Factor kappa-B (NF-kappaB) signaling pathway in controlling expression of IL-7Ralpha in new T cells. Perturbations to NF-kappaB signaling, either by deletion of Inhibitor of Kappa-B Kinase-2 (IKK2) or by inhibiting Rel dimer activity, prevented normal IL-7Ralpha expression in new T cells. Defective IL-7Ralpha expression resulted in impaired survival and homeostatic cell division responses by T cells that could be attributed to their failure to express IL-7Ralpha normally. Surprisingly, NF-kappaB signaling was only required transiently in new T cells to allow their normal expression of IL-7Ralpha, because IKK2 deletion in mature T cells had no effect on IL-7Ralpha expression or their normal homeostatic responsiveness. Therefore, we identify a developmental function for NF-kappaB signaling in the homeostatic maturation of new T cells, by regulating IL-7Ralpha expression. |
