IKK? is required for the homeostasis of regulatory T cells and for the expansion of both regulatory and effector CD4 T cells.

ABSTRACT: It was reported that TNF receptor type II signaling, which has the capacity to stimulate CD4+ forkhead box P3+ (Foxp3+) regulatory T cells (Tregs), activated the noncanonical NF-?B pathway in an IKK?-dependent manner. Therefore, we studied the role of IKK? in the homeostasis of Treg population. To this end, we generated a mouse strain with conditional knockout of IKK? in CD4 cells (Ikk?(f/f):CD4.Cre) that showed a >60% reduction in the number of Tregs in the thymus and peripheral lymphoid tissues, whereas the number of Foxp3- effector T cells (Teffs) remained at a normal level. The function of Tregs deficient in IKK? was examined using Rag1(-/-) mice cotransferred with naive CD4 cells (nCD4s). Although wild-type (WT) Tregs inhibited colitis induced by transfer of WT nCD4s, IKK?-deficient Tregs failed to do so, which was associated with their inability to reconstitute Rag1(-/-) mice. Furthermore, nCD4s deficient in IKK? also failed to reconstitute Rag1(-/-) mice and were defective in proliferative responses in vitro and in vivo. Thus, our study reveals a novel role of IKK? in the maintenance of a normal Treg population and in the control of expansion of CD4 T cells. These properties of IKK? may be exploited as therapeutic strategies in the treatment of major human diseases.

SUBMITTER: Chen X 

PROVIDER: S-EPMC4314223 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature