Huge thanks to all co-authors, institutions and funders!
Sapienza Università di Roma, Fondazione AIRC per la ricerca sul cancro, Istituto Pasteur Italia

In summary, TNF-TNFR2 signal sustains Tregs not through a pure autocrine mechanism. Rather, two Treg subpopulations exist that preferentially express TNFR2 or TNF, which cooperate in enforcing Treg suppression.

TNFR2+ Tregs displayed stronger suppressive suppression and survival, together with higher resistance to oxidative stress (induced with menadione), and less intracellular ROS content, from spleen and tumors.

TNFR2+ and TNF+ Tregs partially maintained their phenotype when cultured in vitro. However, when cocultured, the TNFR2+ prevailed, and "transmitted" their phenotype (and their dye) to the TNF+ Tregs

We found TNF-producing Tregs in multiple organs in naive mice, as well as in tumors and in animals with arthritis. TNF production was a preferential feature of those Tregs not expressing the TNFR2.