Silvia Piconese

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.

TNF Production or TNFR2 Expression Characterize Distinct States of Regulatory T Cells that Cooperate in Treg Expansion in Cancer and Chronic Inflammation Tregs exist in two functional states: TNF-producing Tregs, which are expanded in mouse models of chronic inflammation and cancer, and TNFR2-expressing Tregs, which dominate and transmit their phenoty...

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...