ArticleImmunology2016
SHARPIN controls the development of regulatory T cells.
Article in Immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- The Met1-Ub System in T Cells: What We Know, What We Think We Know.Scandinavian journal of immunology · 2026Review
- Review
- Dysregulated Immune Responses in Sepsis: Insights From Treg-Related Gene Expression.Journal of inflammation research · 2025Article
- Synergistic involvement of the NZF domains of the LUBAC accessory subunits HOIL-1L and SHARPIN in the regulation of LUBAC function.Cell death & disease · 2024Article
- Identification and molecular analysis of RNF31 Q622H germline polymorphism.Oncology letters · 2022Article
- SHARPIN: Role in Finding NEMO and in Amyloid-Beta Clearance and Degradation (ABCD) Pathway in Alzheimer's Disease?Cellular and molecular neurobiology · 2022Review
- Met1-linked ubiquitin signalling in health and disease: inflammation, immunity, cancer, and beyond.Cell death and differentiation · 2021Review
- Ubiquitin-Dependent Regulation of Treg Function and Plasticity.Advances in experimental medicine and biology · 2021Article
- Post-Translational Regulations of Foxp3 in Treg Cells and Their Therapeutic Applications.Frontiers in immunology · 2021Review
- Shank-associated RH domain interactor signaling in tumorigenesis.Oncology letters · 2020Review
- Modulation of autoimmune pathogenesis by T cell-triggered inflammatory cell death.Nature communications · 2019Article
- Tumour necrosis factor signalling in health and disease.F1000Research · 2019Review
- SHARPIN stabilizes estrogen receptor α and promotes breast cancer cell proliferation.Oncotarget · 2017Article
- Hepatitis B virus X protein influences enrichment profiles of H3K9me3 on promoter regions in human hepatoma cell lines.Oncotarget · 2016Article
- Distinct role of IL-1β in instigating disease in SharpinScientific reports · 2016Article
- Linear ubiquitin chain assembly complex coordinates late thymic T-cell differentiation and regulatory T-cell homeostasis.Nature communications · 2016Article
- The Deubiquitinase OTULIN Is an Essential Negative Regulator of Inflammation and Autoimmunity.Cell · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SHARPIN is an essential component of the linear ubiquitin chain assembly complex (LUBAC) complex that controls signalling pathways of various receptors, including the tumour necrosis factor receptor (TNFR), Toll-like receptor (TLR) and antigen receptor, in part by synthesis of linear, non-degrading ubiquitin chains. Consistent with SHARPIN's function in different receptor pathways, the phenotype of SHARPIN-deficient mice is complex, including the development of inflammatory systemic and skin diseases, the latter of which depend on TNFR signal transduction. Given the established function of SHARPIN in primary and malignant B cells, we hypothesized that SHARPIN might also regulate T-cell receptor (TCR) signalling and thereby control T-cell biology. Here, we focus primarily on the role of SHARPIN in T cells, specifically regulatory T (Treg) cells. We found that SHARPIN-deficient (Sharpin(cpdm/cpdm) ) mice have significantly reduced numbers of FOXP3(+) Treg cells in lymphoid organs and the peripheral blood. Competitive reconstitution of irradiated mice with mixed bone marrow from wild-type and SHARPIN-deficient mice revealed an overall reduced thymus population with SHARPIN-deficient cells with almost complete loss of thymic Treg development. Consistent with this cell-intrinsic function of SHARPIN in Treg development, TCR stimulation of SHARPIN-deficient thymocytes revealed reduced activation of nuclear factor-κB and c-Jun N-terminal kinase, establishing a function of SHARPIN in TCR signalling, which may explain the defective Treg development. In turn, in vitro generation and suppressive activity of mature SHARPIN-deficient Treg cells were comparable to wild-type cells, suggesting that maturation, but not function, of SHARPIN-deficient Treg cells is impaired. Taken together, these findings show that SHARPIN controls TCR signalling and is required for efficient generation of Treg cells in vivo, whereas the inhibitory function of mature Treg cells appears to be independent of SHARPIN.
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Registered trials
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.