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Article Dans Une Revue European Journal of Immunology Année : 2020

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

Résumé

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.

Domaines

Immunologie
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Origine : Publication financée par une institution

Dates et versions

inserm-03272271 , version 1 (04-03-2020)
inserm-03272271 , version 2 (28-06-2021)

Identifiants

Citer

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, 2020, 50 (7), pp.972-985. ⟨10.1002/eji.201948393⟩. ⟨inserm-03272271v2⟩
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