ArticleBMC biochemistry2011
Signal peptide cleavage is essential for surface expression of a regulatory T cell surface protein, leucine rich repeat containing 32 (LRRC32).
Article in BMC biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Unraveling the causal role of TGF-βRII in osteoporosis and the potential of its associated differential genes as novel targets.European journal of medical research · 2025Article
- GARP as a Therapeutic Target for the Modulation of Regulatory T Cells in Cancer and Autoimmunity.Frontiers in immunology · 2022Review
- GARP as an Immune Regulatory Molecule in the Tumor Microenvironment of Glioblastoma Multiforme.International journal of molecular sciences · 2019Article
- CD4Immunology · 2017Article
- Eda haplotypes in three-spined stickleback are associated with variation in immune gene expression.Scientific reports · 2017Article
- Differentiation of human monocytes and derived subsets of macrophages and dendritic cells by the HLDA10 monoclonal antibody panel.Clinical & translational immunology · 2016Article
- A large-scale genetic analysis reveals a strong contribution of the HLA class II region to giant cell arteritis susceptibility.American journal of human genetics · 2015Article
- Mesenchymal stromal cells express GARP/LRRC32 on their surface: effects on their biology and immunomodulatory capacity.Stem cells (Dayton, Ohio) · 2015Article
- Current and potential immune therapies and vaccines in the management of psoriasis.Human vaccines & immunotherapeutics · 2014Review
- Infection with feline immunodeficiency virus directly activates CD4+ CD25+ T regulatory cells.Journal of virology · 2013Article
- Th17 responses in chronic allergic airway inflammation abrogate regulatory T-cell-mediated tolerance and contribute to airway remodeling.Mucosal immunology · 2013Article
- A cleavable N-terminal signal peptide promotes widespread olfactory receptor surface expression in HEK293T cells.PloS one · 2013Article
- BK potassium channel modulation by leucine-rich repeat-containing proteins.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Regulation generation: the suppressive functions of human regulatory T cells.Critical reviews in immunology · 2012Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundElevated numbers of regulatory T cells (T(regs)) have been implicated in certain cancers. Depletion of T(regs) has been shown to increase anti-tumor immunity. T(regs) also play a critical role in the suppression of autoimmune responses. The study of T(regs) has been hampered by a lack of adequate surface markers. Leucine Rich Repeat Containing 32 (LRRC32), also known as Glycoprotein A Repetitions Predominant (GARP), has been postulated as a novel surface marker of activated T(regs). However, there is limited information regarding the processing of LRRC32 or the regulatory phenotype and functional activity of T(regs) expressing LRRC32.
resultsUsing naturally-occurring freshly isolated T(regs), we demonstrate that low levels of LRRC32 are present intracellularly prior to activation and that freshly isolated LRRC32+ T(regs) are distinct from LRRC32- T(regs) with respect to the expression of surface CD62L. Using LRRC32 transfectants of HEK cells, we demonstrate that the N-terminus of LRRC32 is cleaved prior to expression of the protein at the cell surface. Furthermore, we demonstrate using a construct containing a deleted putative signal peptide region that the presence of a signal peptide region is critical to cell surface expression of LRRC32. Finally, mixed lymphocyte assays demonstrate that LRRC32+ T(regs) are more potent suppressors than LRRC32- T(regs).
conclusionsA cleaved signal peptide site in LRRC32 is necessary for surface localization of native LRRC32 following activation of naturally-occurring freshly-isolated regulatory T cells. LRRC32 expression appears to alter the surface expression of activation markers of T cells such as CD62L. LRRC32 surface expression may be useful as a marker that selects for more potent T(reg) populations. In summary, understanding the processing and expression of LRRC32 may provide insight into the mechanism of action of T(regs) and the refinement of immunotherapeutic strategies aimed at targeting these cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.