Publication Date:
2015-02-04
Description:
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 α -dependent manner. Therefore, we studied the role of IKK α in the homeostasis of Treg population. To this end, we generated a mouse strain with conditional knockout of IKK α in CD4 cells ( Ikkα 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 α 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 α -deficient Tregs failed to do so, which was associated with their inability to reconstitute Rag1 –/– mice. Furthermore, nCD4s deficient in IKK α 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 α in the maintenance of a normal Treg population and in the control of expansion of CD4 T cells. These properties of IKK α may be exploited as therapeutic strategies in the treatment of major human diseases.—Chen, X., Willette-Brown, J., Wu, X., Hu, Y., Howard, O. M. Z., Hu, Y., Oppenheim, J. J. IKK α is required for the homeostasis of regulatory T cells and for the expansion of both regulatory and effector CD4 T cells.
Print ISSN:
0892-6638
Electronic ISSN:
1530-6860
Topics:
Biology
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