ArticleNature immunology2016
SHARPIN controls regulatory T cells by negatively modulating the T cell antigen receptor complex.
Article in Nature immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 57 citations in OpenAlex.
- SHARPIN restrains IL-33 release by stromal cells to control ILC2 inflammation.Science advances · 2026Article
- Promising TNF-α inhibitors: Targeting pathogenic TNF-α/TNFR signaling to restore Th17/Treg balance in rheumatoid arthritis.Journal of pharmaceutical analysis · 2026Review
- Monogenic disorders of the TNF signalling pathway.Nature reviews. Rheumatology · 2026Review
- 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
- The role of ubiquitination in health and disease.MedComm · 2024Review
- Biallelic human SHARPIN loss of function induces autoinflammation and immunodeficiency.Nature immunology · 2024Article
- SHARPIN: Role in Finding NEMO and in Amyloid-Beta Clearance and Degradation (ABCD) Pathway in Alzheimer's Disease?Cellular and molecular neurobiology · 2022Review
- K63 ubiquitination in immune signaling.Trends in immunology · 2022Review
- The Interactions Between Autoinflammation and Type 2 Immunity: From Mechanistic Studies to Epidemiologic Associations.Frontiers in immunology · 2022Review
- Dual roles for LUBAC signaling in thymic epithelial cell development and survival.Cell death and differentiation · 2021Article
- SHARPIN regulates the development of clear cell renal cell carcinoma by promoting von Hippel-Lindau protein ubiquitination and degradation.Cancer science · 2021Article
- The deubiquitinase CYLD controls protective immunity against helminth infection by regulation of Treg cell plasticity.The Journal of allergy and clinical immunology · 2021Article
- Met1-linked ubiquitin signalling in health and disease: inflammation, immunity, cancer, and beyond.Cell death and differentiation · 2021Review
- Article
- Post-Translational Regulations of Foxp3 in Treg Cells and Their Therapeutic Applications.Frontiers in immunology · 2021Review
- Global Screening of LUBAC and OTULIN Interacting Proteins by Human Proteome Microarray.Frontiers in cell and developmental biology · 2021Article
- Ubiquitin-Dependent Regulation of Treg Function and Plasticity.Advances in experimental medicine and biology · 2021Article
- Integrin Binding Dynamics Modulate Ligand-Specific Mechanosensing in Mammary Gland Fibroblasts.iScience · 2020Article
- Modulation of autoimmune pathogenesis by T cell-triggered inflammatory cell death.Nature communications · 2019Article
- Integrative proteomics reveals an increase in non-degradative ubiquitylation in activated CD4Nature immunology · 2019Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
SHARPIN forms a linear-ubiquitin-chain-assembly complex that promotes signaling via the transcription factor NF-κB. SHARPIN deficiency leads to progressive multi-organ inflammation and immune system malfunction, but how SHARPIN regulates T cell responses is unclear. Here we found that SHARPIN deficiency resulted in a substantial reduction in the number of and defective function of regulatory T cells (Treg cells). Transfer of SHARPIN-sufficient Treg cells into SHARPIN-deficient mice considerably alleviated their systemic inflammation. SHARPIN-deficient T cells displayed enhanced proximal signaling via the T cell antigen receptor (TCR) without an effect on the activation of NF-κB. SHARPIN conjugated with Lys63 (K63)-linked ubiquitin chains, which led to inhibition of the association of TCRζ with the signaling kinase Zap70; this affected the generation of Treg cells. Our study therefore identifies a role for SHARPIN in TCR signaling whereby it maintains immunological homeostasis and tolerance by regulating Treg cells.
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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.