Journal article
The TNF Receptor Superfamily-NF-κB Axis Is Critical to Maintain Effector Regulatory T Cells in Lymphoid and Non-lymphoid Tissues
A Vasanthakumar, Y Liao, P Teh, MF Pascutti, AE Oja, AL Garnham, R Gloury, JC Tempany, T Sidwell, E Cuadrado, P Tuijnenburg, TW Kuijpers, N Lalaoui, LA Mielke, VL Bryant, PD Hodgkin, J Silke, GK Smyth, MA Nolte, W Shi Show all
Cell Reports | CELL PRESS | Published : 2017
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-κB transcription factor RelA, which was required to maintain eTreg cells in lymphoid and non-lymphoid tissues, including RORγt+ Treg cells in the small intestine. In response to TNFRSF signaling, RelA regulated basic cellular processes, including ce..
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Awarded by CSL Behring
Funding Acknowledgements
This work was supported by NHMRC project grants (#1069075 and #1106378 to A.K.), the Sylvia and Charles Viertel Foundation (fellowship to A.K.), a Walter and Eliza Institute Centenary Fellowship funded by the CSL (to W.S.), and the Landsteiner Foundation for Blood Transfusion Research (LSBR grant #1014 to M.A.N.), and the Center of Immunodeficiencies Amsterdam (to P. Tuijnenburg). V.L.B. and P.D.H. are supported by NHMRC program grant #1054925 and project grant #1127198. P. Teh is supported by a scholarship from Kidney Health Australia. J.C.T. is supported by an Australian Government Research Training Program Postgraduate Scholarship. We thank Drs. Ashish Banerjee and George Grigoriadis for discussions at the early stages of the project and Dr. Joanna Groom for her help in preparing the histology slides.