2. Academic Validation
  3. CD4+ regulatory T cells lacking Helios and Eos

CD4+ regulatory T cells lacking Helios and Eos

  • Biochem Biophys Res Commun. 2023 Sep 24:674:83-89. doi: 10.1016/j.bbrc.2023.06.087.
Katarzyna Polak 1,  Patricia Marchal 1,  Chiara Taroni 1,  Claudine Ebel 2,  Peggy Kirstetter 1,  Philippe Kastner 3,  Susan Chan 4
Affiliations

Affiliations

  • 1 Université de Strasbourg, IGBMC UMR 7104- UMR-S 1258, F-67400 Illkirch, France; CNRS, UMR 7104, F-67400 Illkirch, France; Inserm, UMR-S 1258, F-67400 Illkirch, France; IGBMC, Institut de Génétique et de Biologie Moléculaire et Cellulaire, F-67400 Illkirch, France.
  • 2 Université de Strasbourg, IGBMC UMR 7104- UMR-S 1258, F-67400 Illkirch, France; CNRS, UMR 7104, F-67400 Illkirch, France; Inserm, UMR-S 1258, F-67400 Illkirch, France; IGBMC, Institut de Génétique et de Biologie Moléculaire et Cellulaire, F-67400 Illkirch, France; Flow Cytometry Service, IGBMC, Illkirch, France.
  • 3 Université de Strasbourg, IGBMC UMR 7104- UMR-S 1258, F-67400 Illkirch, France; CNRS, UMR 7104, F-67400 Illkirch, France; Inserm, UMR-S 1258, F-67400 Illkirch, France; IGBMC, Institut de Génétique et de Biologie Moléculaire et Cellulaire, F-67400 Illkirch, France; Faculté de Médecine, Université de Strasbourg, Strasbourg, France. Electronic address: [email protected].
  • 4 Université de Strasbourg, IGBMC UMR 7104- UMR-S 1258, F-67400 Illkirch, France; CNRS, UMR 7104, F-67400 Illkirch, France; Inserm, UMR-S 1258, F-67400 Illkirch, France; IGBMC, Institut de Génétique et de Biologie Moléculaire et Cellulaire, F-67400 Illkirch, France. Electronic address: [email protected].
PMID: 37413709 DOI: 10.1016/j.bbrc.2023.06.087
Abstract

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.

Keywords

Aging; Functional specificity; Helios and Eos transcription factors; Knock-out mouse models; Regulatory T cells.

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