GSE98262
The TNF receptor super family - NF-?B axis is critical to maintain effector regulatory T cells in lymphoid and non-lymphoid tissues [RNA-seq]
After exiting the thymus, Foxp3+ regulatory T (Treg) cells undergo further differentiation in the periphery resulting in the generation of effector (e)Treg cells, a process dependent on TCR signaling and the transcription factor IRF4. Here we show tumor necrosis factor receptor super family (TNFRSF) signaling plays a crucial role in the development and maintenance of eTreg cells. TNFRSF signaling activated the NF-?B transcription factor RelA and induced expansion and survival of eTreg cells in lymphoid and non-lymphoid tissues, including ROR?t+ resident Treg cells in the small intestine. RelA regulated basic cellular processes in Treg cells, including cell survival and proliferation in response to TNFRSF signaling, but was not required for IRF4 expression or DNA binding, indicating that both pathways operate independently. Importantly, a similar pathway appeared to be active in humans, as patients with a point mutation in NF-?B1, a binding partner of RelA, had severely compromised Treg cells. Therefore, although TCR signaling is essential for eTreg cell differentiation, the TNFRSF-NF-?B axis was additionally required in a non-redundant manner to maintain the pool of eTreg cells. Overall design: Transcriptional profiling of WT and RelA/p65-deficient Treg cells (from steady state mice).