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Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
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CD4+ regulatory T cells lacking Helios and Eos.

Katarzyna Polak1, Patricia Marchal1, Chiara Taroni1

  • 1Université 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.

Biochemical and Biophysical Research Communications
|July 6, 2023
PubMed
Summary

Helios (Ikzf2) and Eos (Ikzf4) are transcription factors crucial for regulatory T (Treg) cell function. While both are needed for optimal Foxp3 expression, they regulate distinct genes and have non-redundant roles in Treg cell aging and overall function.

Keywords:
AgingFunctional specificityHelios and Eos transcription factorsKnock-out mouse modelsRegulatory T cells

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Regulatory T (Treg) cells are vital for immune homeostasis and preventing autoimmunity.
  • Helios (Ikzf2) and Eos (Ikzf4) are Ikaros family transcription factors highly expressed in Treg cells.
  • Their precise, distinct roles in Treg cell biology are not fully elucidated.

Purpose of the Study:

  • To investigate the specific and potentially redundant functions of Helios and Eos in Treg cell development and function.
  • To determine the impact of combined Helios and Eos deficiency on Treg cell biology.
  • To identify unique roles for each factor in Treg cell maintenance and aging.

Main Methods:

  • Generation and analysis of mice with germline deletions of Ikzf2 and Ikzf4.
  • Assessment of Treg cell differentiation and suppressive function in vitro.
  • Analysis of gene expression profiles regulated by Helios and Eos.
  • Evaluation of Treg cell frequencies in aged mice with Helios or Eos deficiency.

Main Results:

  • Mice lacking both Helios and Eos showed limited differences compared to single knockout mice.
  • Double knockout Treg cells differentiated normally and suppressed effector T cells effectively in vitro.
  • Both Helios and Eos are necessary for optimal Foxp3 protein levels.
  • Helios and Eos regulate largely distinct sets of genes.
  • Only Helios deficiency led to impaired Treg cell aging, with reduced frequencies in older mice.

Conclusions:

  • Helios and Eos play distinct, non-redundant roles in Treg cell biology.
  • While both contribute to Treg cell function and Foxp3 expression, their regulatory targets differ significantly.
  • Helios has a unique role in maintaining Treg cell populations during aging.