NF-?B signaling mediates homeostatic maturation of new T cells.

ABSTRACT: Interleukin (IL)-7 is critical for the maintenance of the peripheral T-cell compartment of the adaptive immune system. IL-7 receptor ? (IL-7R?) 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 ?-B (NF-?B) signaling pathway in controlling expression of IL-7R? in new T cells. Perturbations to NF-?B signaling, either by deletion of Inhibitor of Kappa-B Kinase-2 (IKK2) or by inhibiting Rel dimer activity, prevented normal IL-7R? expression in new T cells. Defective IL-7R? expression resulted in impaired survival and homeostatic cell division responses by T cells that could be attributed to their failure to express IL-7R? normally. Surprisingly, NF-?B signaling was only required transiently in new T cells to allow their normal expression of IL-7R?, because IKK2 deletion in mature T cells had no effect on IL-7R? expression or their normal homeostatic responsiveness. Therefore, we identify a developmental function for NF-?B signaling in the homeostatic maturation of new T cells, by regulating IL-7R? expression.

SUBMITTER: Silva A 

PROVIDER: S-EPMC3948292 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature