Eomes controls the development of Th17-derived (non-classic) Th1 cells during chronic inflammation

European Journal of Immunology
Alessio MazzoniFrancesco Annunziato

Abstract

It is well accepted that Th17 cells are a highly plastic cell subset that can be easily directed toward the Th1 phenotype in vitro and also in vivo during inflammation. However, there is an ongoing debate regarding the reverse plasticity (conversion from Th1 to Th17). We show here that ectopic ROR-γt expression can restore or initiate IL-17 expression by non-classic or classic Th1 cells, respectively, while common pro-Th17 cytokine cocktails are ineffective. This stability of the Th1 phenotype is at least partially due to the presence of a molecular machinery governed by the transcription factor Eomes, which promotes IFN-γ secretion while inhibiting the expression of ROR-γt and IL-17. By using a mouse model of T cell-dependent colitis we demonstrate that Eomes controls non-classic Th1 cell development also in vivo and promotes their pathogenic potential. Eomes expression associates to a highly inflammatory phenotype also in patients with juvenile idiopathic arthritis. Indeed, it favors the acquisition of a cytotoxic signature, and promotes the development of IFN-γ+ GM-CSF+ cells that have been described to be pathogenic in chronic inflammatory disorders.

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Citations

Oct 1, 2019·Immunology·Alessio MazzoniFrancesco Annunziato
May 23, 2020·European Journal of Immunology·Alessio MazzoniFrancesco Annunziato
Sep 13, 2019·Modern Rheumatology·Jan LeipeAlla Skapenko
Oct 2, 2019·Frontiers in Immunology·Martina Di GiovangiulioMassimo C Fantini
Apr 2, 2019·Frontiers in Immunology·Laura MaggiLorenzo Cosmi
Oct 22, 2019·European Journal of Immunology·Andrea CossarizzaArturo Zychlinsky
Dec 10, 2020·European Journal of Immunology·Patrick MaschmeyerMir-Farzin Mashreghi
Dec 12, 2018·European Journal of Immunology·Anne S DejeanThierry Walzer
Apr 8, 2021·Nature Reviews. Rheumatology·Patrick MaschmeyerAndreas Radbruch
Oct 17, 2020·Immunology·Silvia CerboniSuman Mitra
Jun 9, 2021·Reproductive Sciences·Dan LiYeling Wang
Sep 29, 2021·Gastroenterology·Emory ZitelloYouping Deng

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