Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP

Eyad Elkord, May Abd Al Samid, Belal Chaudhary

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41 Citations (Scopus)

Abstract

Regulatory T cells (Tregs) are key players of immune regulation/dysregulation both in physiological and pathophysiological settings. Despite significant advances in understanding Treg function, there is still a pressing need to define reliable and specific markers that can distinguish different Treg subpopulations. Herein we show for the first time that markers of activated Tregs [latency associated peptide (LAP) and glycoprotein A repetitions predominant (GARP, or LRRC32)] are expressed on CD4+FoxP3- T cells expressing Helios (FoxP3-Helios+) in the steady state. Following TCR activation, GARP/LAP are up-regulated on CD4+Helios+ T cells regardless of FoxP3 expression (FoxP3+/-Helios+). We show that CD4+GARP+/-LAP+ Tregs make IL-10 immunosuppressive cytokine but not IFN-γ effector cytokine. Further characterization of FoxP3/Helios subpopulations showed that FoxP3+Helios+ Tregs proliferate in vitro significantly less than FoxP3+Helios- Tregs upon TCR stimulation. Unlike FoxP3+Helios- Tregs, FoxP3+Helios+ Tregs secrete IL-10 but not IFN-γ or IL-2, confirming they are bona fide Tregs with immunosuppressive characteristics. Taken together, Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP, and FoxP3+Helios+ Tregs have more suppressive characteristics, compared with FoxP3+Helios- Tregs. Our work implies that therapeutic modalities for treating autoimmune and inflammatory diseases, allergies and graft rejection should be designed to induce and/or expand FoxP3+Helios+ Tregs, while therapies against cancers or infectious diseases should avoid such expansion/induction.

Original languageEnglish
Pages (from-to)20026-20036
Number of pages11
JournalOncotarget
Volume6
Issue number24
Publication statusPublished - 2015
Externally publishedYes

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Keywords

  • FoxP3
  • GARP/LAP
  • Helios
  • Immune response
  • Immunity
  • Immunology and microbiology section
  • Regulatory T cells

ASJC Scopus subject areas

  • Oncology

Cite this

Elkord, E., Al Samid, M. A., & Chaudhary, B. (2015). Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP. Oncotarget, 6(24), 20026-20036.