Expression of GARP selectively identifies activated human FOXP3+ regulatory T cells

@article{Wang2009ExpressionOG,
  title={Expression of GARP selectively identifies activated human FOXP3+ regulatory T cells},
  author={Rui Wang and Lina Kozhaya and Frances Mercer and Alka Khaitan and Hodaka Fujii and Derya Unutmaz},
  journal={Proceedings of the National Academy of Sciences},
  year={2009},
  volume={106},
  pages={13439 - 13444}
}
The molecules that define human regulatory T cells (Tregs) phenotypically and functionally remain to be fully characterized. We recently showed that activated human Tregs express mRNA for a transmembrane protein called glycoprotein A repetitions predominant (GARP, or LRRC32). Here, using a GARP-specific mAb, we demonstrate that expression of GARP on activated Tregs correlates with their suppressive capacity. However, GARP was not induced on T cells activated in the presence of TGFβ, which… 
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GARP–TGF-β Complexes Negatively Regulate Regulatory T Cell Development and Maintenance of Peripheral CD4+ T Cells In Vivo

A role for GARP is suggested in natural and induced Treg development through activation of bound latent TGF-β and signaling, which negatively regulates GARP expression on Tregs.

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

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.

Helios Expression Is a Marker of T Cell Activation and Proliferation

Investigation of Helios expression in murine and human T cells under resting or activating conditions, using well-characterized molecules of naïve/effector/memory phenotypes, as well as a set of Treg-associated markers found that Helios-negative T cells are enriched for naïve T cell phenotypes and vice versa.

FOXP3 Expression in GARP-Transduced Helper T Cells Is Not Associated with FOXP3 TSDR Demethylation

Although GARP-engineered Th cells exhibit stable FOXP3 expression and a phenotypic reprogramming towards T Reg cells in vitro, these cells do not completely mimic the epigenotype of natural Treg cells and concepts based on the genetic modification of Th cells should be critically tested before any clinical application.

GARP Dampens Cancer Immunity by Sustaining Function and Accumulation of Regulatory T Cells in the Colon.

It is demonstrated that loss of GARP in Treg cells leads to spontaneous inflammation with highly activated CD4+ and CD8+ T cells and development of enteritis, highlighting the importance of cell surface TGFβ in T Reg function and GARP as a potential therapeutic target for colorectal cancer therapy.

The Tregs' world according to GARP

A study provides further demonstration that GARP is selectively expressed only in activated human nT Reg and nTreg cell clones but not in activated effector T cells, confirming GARP as a bona fide nTReg marker.

Impairment of Circulating CD4+CD25+GARP+ Regulatory T Cells in Patients with Acute Coronary Syndrome

It is indicated that circulating CD4+CD25+GARP+ Tregs are impaired in patients with acute coronary syndrome, and targeting GARP may promote the protective function of T Regs in ACS.

Human treg cells are characterized by low/negative CD6 expression

Evidence is presented that CD4+CD25hi CD6lo/− nTreg have high expression of FOXP3and exhibit in vitro suppressive activity on CD8+ T‐cell proliferation, providing a new tool for the identification of nT Reg cells without recourse to intracellular staining, and for the purification of these cells by negative selection.

Regulation of the Expression of GARP/Latent TGF-β1 Complexes on Mouse T Cells and Their Role in Regulatory T Cell and Th17 Differentiation

GARP-deficient Tregs develop normally, are present in normal numbers in peripheral tissues, and are fully competent suppressors of the activation of conventional T cells in vitro.

The expression of CD39 on regulatory T cells is genetically driven and further upregulated at sites of inflammation.

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