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Helios Enhances Treg Cell Function in Cooperation With FoxP3.

Hiroaki Takatori1, Hirotoshi Kawashima1, Ayako Matsuki1

  • 1Chiba University Graduate School of Medicine, Chiba, Japan.

Arthritis & Rheumatology (Hoboken, N.J.)
|March 4, 2015
PubMed
Summary

Helios enhances regulatory T cell (Treg) function in autoimmune diseases by cooperating with FoxP3. Interleukin-6 (IL-6) inhibits Helios+ Treg cell development, while Tocilizumab treatment increases Helios expression in rheumatoid arthritis patients.

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Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Helios+ Treg cells are implicated in autoimmune disease regulation.
  • Mechanisms governing Helios+ Treg cell development and function are not fully understood.

Purpose of the Study:

  • To investigate the regulatory mechanisms of Helios expression in CD4+ T cells.
  • To determine the role of Helios in transforming growth factor β (TGFβ)-induced Treg cell function.

Main Methods:

  • DNA microarray analysis of Helios expression in rheumatoid arthritis patients before and after biologic treatment.
  • Assessment of interleukin-6 (IL-6) and TGFβ effects on Helios expression in human and mouse CD4+ T cells.
  • Evaluation of forced Helios expression and FoxP3 deficiency on induced Treg cell function.

Main Results:

  • Tocilizumab treatment increased Helios expression in responsive rheumatoid arthritis patients.
  • IL-6 inhibited TGFβ-induced Helios+ Treg cell development in humans and mice.
  • Helios expression requires cell-intrinsic FoxP3 and TGFβ signaling, enhancing Treg cell suppressive function.

Conclusions:

  • Helios enhances induced Treg cell function synergistically with FoxP3.
  • Understanding Helios regulation offers potential therapeutic insights for autoimmune diseases.