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.

Tregs can choose between producing TNF or sensing TNFR2... and the two states are much different!
See our latest story published in @eurjimmunol.bsky.social

onlinelibrary.wiley.com/doi/10.1002/...

Our study "Iron capture through CD71 drives perinatal and tumor-associated Treg expansion" is available at @jci-insight.bsky.social

insight.jci.org/articles/vie...