Type III interferon primes pDCs for TLR7 activation and antagonizes immune suppression mediated by TGF-β and PGE2

Candice Sakref, Alexis Saby, Céline Rodriguez, Maude Ardin, Lyvia Moudombi, Anne-Claire Doffin, Elisa Gobbini, Aurélien Voissiere, Laurie Besson, Léo Laoubi, Jan Böttcher, Stéphane Depil, Margaux Hubert, Nathalie Bendriss-Vermare, Christophe Caux and Jenny Valladeau-Guilemond ()
Additional contact information
Candice Sakref: CNRS
Alexis Saby: CNRS
Céline Rodriguez: CNRS
Maude Ardin: CNRS
Lyvia Moudombi: CNRS
Anne-Claire Doffin: CNRS
Elisa Gobbini: CNRS
Aurélien Voissiere: CNRS
Laurie Besson: CNRS
Léo Laoubi: CNRS
Jan Böttcher: University of Tübingen
Stéphane Depil: CNRS
Margaux Hubert: CNRS
Nathalie Bendriss-Vermare: CNRS
Christophe Caux: CNRS
Jenny Valladeau-Guilemond: CNRS

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Conventional dendritic cell and plasmacytoid dendritic cell (pDC) subsets have specialized functions that can be modulated by the tumor microenvironment, and produce different interferons that are central to antitumor immune responses. While the function of type I interferons in tumor immunity is well characterized, that of type III interferons produced by type 1 conventional dendritic cells in the tumor microenvironment remains unclear. Here we demonstrate in vitro that type III interferons orchestrate pDC survival, activation and TLR7 expression in the blood, thereby enhancing pDC responses to a TLR7 ligand. Moreover, we show that tumor-associated pDCs express the highest level of IFNLR1, and that these immune cell subsets are the most responsive to IFN-III. Importantly, type III interferons prevent the inhibition of pDCs induced by TGF-β or PGE2 in tumor soluble milieu from patients to restores production of IFN-α in pDCs. With TGF-β or PGE2 having pleotropic functions in immune regulation, our results thus implicate IFN-III-mediated immune modulation to have broad impact on various pathological situations.

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58220-8

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DOI: 10.1038/s41467-025-58220-8

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