Our previous studies show that TNF activates and expands Tregs through TNFR2. It was reported that TNF-TNFR2 interaction results in the activation of alternative NFκB pathway through p100 processing, in IKKα-dependent manner. We therefore hypothesize that IKKα may play an important role in determining the size of Treg pool. To this end, we generated a mouse strain with conditional KO of IKKα in CD4 cells (CD4-IKKα-/-) which showed a marked reduction in the number of Tregs and in the proportion of Tregs in CD4 cells, indicating that IKKα KO had more profound impact on Tregs than Teffs. In vitro, naïve CD4 cells deficient in IKKα could be differentiated as usual into Foxp3-expressing cells by TGFβ, suggesting that reduction of Tregs in CD4-IKKα-/- mice was likely due to a defect in the maintenance of the Treg pool, rather than a malfunction in the induction of Foxp3 expression. The function of Tregs deficient in IKKα was examined by co-transfer to Rag1-/- mice together with naïve CD4 cells. Although WT Tregs was able to inhibit colitis induced by transfer of WT naïve CD4 cells, IKKα-deficient Tregs failed to inhibit colitis which was associated with their incapacity to reconstitute in Rag1-/- mice. Nevertheless, naïve CD4 cells deficient in IKKα also failed to reconstitute Rag1-/- mice. Therefore, our study indicate that IKKα is important for the maintenance of normal Treg pool and is critical for the expansion of Treg cells as well as Teff cells.
- Copyright © 2013 by The American Association of Immunologists, Inc.