| First Author | Chen X | Year | 2015 |
| Journal | FASEB J | Volume | 29 |
| Issue | 2 | Pages | 443-54 |
| PubMed ID | 25376833 | Mgi Jnum | J:218224 |
| Mgi Id | MGI:5617000 | Doi | 10.1096/fj.14-259564 |
| Citation | Chen X, et al. (2015) IKKalpha is required for the homeostasis of regulatory T cells and for the expansion of both regulatory and effector CD4 T cells. FASEB J 29(2):443-54 |
| abstractText | 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-kappaB pathway in an IKKalpha-dependent manner. Therefore, we studied the role of IKKalpha in the homeostasis of Treg population. To this end, we generated a mouse strain with conditional knockout of IKKalpha in CD4 cells (Ikkalpha(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 IKKalpha was examined using Rag1(-/-) mice cotransferred with naive CD4 cells (nCD4s). Although wild-type (WT) Tregs inhibited colitis induced by transfer of WT nCD4s, IKKalpha-deficient Tregs failed to do so, which was associated with their inability to reconstitute Rag1(-/-) mice. Furthermore, nCD4s deficient in IKKalpha 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 IKKalpha in the maintenance of a normal Treg population and in the control of expansion of CD4 T cells. These properties of IKKalpha 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. IKKalpha is required for the homeostasis of regulatory T cells and for the expansion of both regulatory and effector CD4 T cells. |
