Membrane protein GARP is a receptor for latent TGF‐β on the surface of activated human Treg
Open accessAbstract
Human Treg and Th clones secrete the latent form of TGF‐β, in which the mature TGF‐β protein is bound to the latency‐associated peptide (LAP), and is thereby prevented from binding to the TGF‐β receptor. We previously showed that upon TCR stimulation, human Treg clones but not Th clones produce active TGF‐β and bear LAP on their surface. Here, we show that latent TGF‐β, i.e. both LAP and mature TGF‐β, binds to glycoprotein A repetitions predominant (GARP), a transmembrane protein containing leucine rich repeats, which is present on the surface of stimulated Treg clones but not on Th clones. Membrane localization of latent TGF‐β mediated by binding to GARP may be necessary for the ability of Treg to activate TGF‐β upon TCR stimulation. However, it is not sufficient as lentiviral‐mediated expression of GARP in human Th cells induces binding of latent TGF‐β to the cell surface, but does not result in the production of active TGF‐β upon stimulation of these Th cells.
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At the protein level, LRRC32 is known to regulate T-cell proliferation, cytokine secretion, and TGF-β activation.
“At the protein level, LRRC32 is known to regulate T-cell proliferation, cytokine secretion, and TGF-β activation.492”
From International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (2018) · cites this paper as [492]
The Discussion (page not available in our copy) links GARP, the LRRC32 protein, to production of active TGF-β in stimulated human Treg cells, but does not establish that GARP alone activates it. The same section reports no decrease in T-cell proliferation after GARP overexpression, and the paper does not show that GARP regulates cytokine secretion. (LLM, conf=0.87)
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References 28 · Cited by 252
Research works printed but not linked: 1
- e-mail: sophie.lucas@uclouvain.be See accompanying Commentary: http://dx.doi.org/10.1002/eji.200940117 Supporting Information for this article is available at www.wiley-vch.de/contents/jc_2040/2009/39684_s.pdf · DOI
- Authors
- Stockis, J., Colau, D., Coulie, P. G., & Lucas, S.
- Affiliations
- de Duve Institute (BE)
- Ludwig Cancer Research (BE)
- Corresponding author
- Lucas, Sophie
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 2009-12
- Volume
- 39
- Issue
- 12
- Pages
- 3315-3322
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- OpenAlex
- W2091167995
- Cited by
- 252
- References
- 28
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 14 · 2023: 12 · 2022: 21 · 2021: 20 · 2020: 12 · 2019: 11 · 2018: 12 · 2017: 20 · 2016: 15 · 2015: 21 · 2014: 23 · 2013: 21 · 2012: 14
- FWCI
- 5.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- GARP, latent TGF-beta, TGF-beta receptor, regulatory T cells, T helper cells, latency-associated peptide, T cell receptor stimulation, TGF-beta activation, cell surface receptors, leucine-rich repeats, lentiviral transduction
- MeSH terms
- Cell Membrane, Cells, Cultured, Flow Cytometry, Humans, Lymphocyte Activation, Membrane Proteins, Models, Biological, Protein Binding, T-Lymphocytes, Blotting, Western, CD4 Antigens, Transforming Growth Factor beta, Muromonab-CD3, Jurkat Cells, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes, Regulatory, Interleukin-2 Receptor alpha Subunit, Interleukin-7 Receptor alpha Subunit, Latent TGF-beta Binding Proteins
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