CD4 regulatory T cells lacking Helios and Eos.
Fiche publication
Date publication
juin 2023
Journal
Biochemical and biophysical research communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHAN Susan, Mme EBEL Claudine, Dr KASTNER Philippe, Dr KIRSTETTER Peggy
Tous les auteurs :
Polak K, Marchal P, Taroni C, Ebel C, Kirstetter P, Kastner P, Chan S
Lien Pubmed
Résumé
The transcriptional regulators that drive regulatory T (Treg) cell development and function remain partially understood. Helios (Ikzf2) and Eos (Ikzf4) are closely-related members of the Ikaros family of transcription factors. They are highly expressed in CD4 Treg cells and functionally important for Treg cell biology, as mice deficient for either Helios or Eos are susceptible to autoimmune diseases. However, it remains unknown if these factors exhibit specific or partially redundant functions in Treg cells. Here we show that mice with germline deletions of both Ikzf2 and Ikzf4 are not very different from animals with single Ikzf2 or Ikzf4 deletions. Double knockout Treg cells differentiate normally, and efficiently suppress effector T cell proliferation in vitro. Both Helios and Eos are required for optimal Foxp3 protein expression. Surprisingly, Helios and Eos regulate different, largely non-overlapping, sets of genes. Only Helios is required for proper Treg cell aging, as Helios deficiency results in reduced Treg cell frequencies in the spleen of older animals. These results indicate that Helios and Eos are required for distinct aspects of Treg cell function.
Mots clés
Aging, Functional specificity, Helios and Eos transcription factors, Knock-out mouse models, Regulatory T cells
Référence
Biochem Biophys Res Commun. 2023 06 28;674:83-89