The TNF Receptor Superfamily-NF-kappaB axis Is critical to maintain effector regulatory T cells in lymphoid and non-lymphoid tissues
- Author(s)
- Vasanthakumar, A; Liao, Y; Teh, P; Pascutti, MF; Oja, AE; Garnham, AL; Gloury, R; Tempany, JC; Sidwell, T; Cuadrado, E; Tuijnenburg, P; Kuijpers, TW; Lalaoui, N; Mielke, LA; Bryant, VL; Hodgkin, PD; Silke, J; Smyth, GK; Nolte, MA; Shi, W; Kallies, A;
- Journal Title
- Cell Reports
- Publication Type
- Journal Article in press
- Abstract
- After exiting the thymus, Foxp3+ regulatory T (Treg) cells undergo further differentiation in the periphery, resulting in the generation of mature, fully suppressive effector (e)Treg cells in a process dependent on TCR signaling and the transcription factor IRF4. Here, we show that tumor necrosis factor receptor superfamily (TNFRSF) signaling plays a crucial role in the development and maintenance of eTreg cells. TNFRSF signaling activated the NF-kappaB transcription factor RelA, which was required to maintain eTreg cells in lymphoid and non-lymphoid tissues, including RORgammat+ Treg cells in the small intestine. In response to TNFRSF signaling, RelA regulated basic cellular processes, including cell survival and proliferation, but was dispensable for IRF4 expression or DNA binding, indicating that both pathways operated independently. Importantly, mutations in the RelA binding partner NF-kappaB1 compromised eTreg cells in humans, suggesting that the TNFRSF-NF-kappaB axis was required in a non-redundant manner to maintain eTreg cells in mice and humans.
- Publisher
- Cell Press
- Research Division(s)
- Molecular Immunology; Bioinformatics; Immunology; Cell Signalling And Cell Death
- PubMed ID
- 28889989
- Publisher's Version
- https://doi.org/10.1016/j.celrep.2017.08.068
- Open Access at Publisher's Site
http://www.sciencedirect.com/science/article/pii/S221112471731210X- NHMRC Grants
- NHMRC/1054925, NHMRC/1127198, NHMRC/1069075, NHMRC/1106378,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2017-09-18 11:59:43
Last Modified: 2017-09-19 03:27:29