title: NF-κB 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 α (IL-7Rα) 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 κ-B (NF-κB) signaling pathway in controlling expression of IL-7Rα in new T cells. Perturbations to NF-κB signaling, either by deletion of Inhibitor of Kappa-B Kinase-2 (IKK2) or by inhibiting Rel dimer activity, prevented normal IL-7Rα expression in new T cells. Defective IL-7Rα expression resulted in impaired survival and homeostatic cell division responses by T cells that could be attributed to their failure to express IL-7Rα normally. Surprisingly, NF-κB signaling was only required transiently in new T cells to allow their normal expression of IL-7Rα, because IKK2 deletion in mature T cells had no effect on IL-7Rα expression or their normal homeostatic responsiveness. Therefore, we identify a developmental function for NF-κB signaling in the homeostatic maturation of new T cells, by regulating IL-7Rα expression.
authors.affiliation: Division of Immune Cell Biology, Medical Research Council National Institute for Medical Research, London, NW7 1AA, United Kingdom.
authors.forename: Ana
authors.initials: A
authors.lastname: Silva
authors.forename: Georgina
authors.initials: G
authors.lastname: Cornish
authors.forename: Steven C
authors.initials: SC
authors.lastname: Ley
authors.forename: Benedict
authors.initials: B
authors.lastname: Seddon
mesh_terms: D000818:Animals; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology*; D015151:Immunoblotting; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020395:Receptors, Interleukin-7 / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: D016328:NF-kappa B; D020395:Receptors, Interleukin-7