Skip to Main content Skip to Navigation
Journal articles

Tumor necrosis factor receptor family costimulation increases regulatory T‐cell activation and function via NF‐κB

Abstract : Several drugs targeting members of the TNF superfamily or TNF receptor superfamily (TNFRSF) are widely used in medicine or are currently being tested in therapeutic trials. However, their mechanism of action remains poorly understood. Here, we explored the effects of TNFRSF co-stimulation on murine Foxp3+ regulatory T cell (Treg) biology, as they are pivotal modulators of immune responses. We show that engagement of TNFR2, 4-1BB, GITR, and DR3, but not OX40, increases Treg proliferation and survival. Triggering these TNFRSF in Tregs induces similar changes in gene expression patterns, suggesting that they engage common signal transduction pathways. Among them, we identified a major role of canonical NF-κB. Importantly, TNFRSF co-stimulation improves the ability of Tregs to suppress colitis. Our data demonstrate that stimulation of discrete TNFRSF members enhances Treg activation and function through a shared mechanism. Consequently, therapeutic effects of drugs targeting TNFRSF or their ligands may be mediated by their effect on Tregs.
Document type :
Journal articles
Complete list of metadata

https://www.hal.inserm.fr/inserm-03272271
Contributor : Gilles Marodon Connect in order to contact the contributor
Submitted on : Monday, June 28, 2021 - 11:27:07 AM
Last modification on : Tuesday, November 16, 2021 - 4:27:33 AM
Long-term archiving on: : Wednesday, September 29, 2021 - 6:56:10 PM

File

eji.201948393.pdf
Publication funded by an institution

Identifiers

Citation

Martina Lubrano Di Ricco, Emilie Ronin, Davi Collares, Jordane Divoux, Sylvie Grégoire, et al.. Tumor necrosis factor receptor family costimulation increases regulatory T‐cell activation and function via NF‐κB. European Journal of Immunology, Wiley-VCH Verlag, 2020, 50 (7), pp.972-985. ⟨10.1002/eji.201948393⟩. ⟨inserm-03272271⟩

Share

Metrics

Record views

35

Files downloads

42