ArticleThe Journal of experimental medicine2013
Shp1 regulates T cell homeostasis by limiting IL-4 signals.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
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Who cites it
61 citing papers in PubMed, 91 citations in OpenAlex.
- PTPN6/SHP-1 in autoimmune disease: immune tolerance, regulatory mechanisms, and therapeutic targeting.Frontiers in immunology · 2026Review
- T lymphocyte-specific deletion of SHP1 and SHP2 promotes activation-induced cell death of CD4Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Shp-1 regulates the activity of low-affinity T cells specific to endogenous self-antigen during melanoma tumor growth and drives resistance to immune checkpoint inhibition.Journal for immunotherapy of cancer · 2025Article
- THEMIS promotes T cell development and maintenance by rising the signaling threshold of the inhibitory receptor BTLA.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- 1-Pyrroline-5-carboxylate inhibit T cell glycolysis in prostate cancer microenvironment by SHP1/PKM2/LDHB axis.Cell communication and signaling : CCS · 2024Article
- Review
- GRB2 promotes thymocyte positive selection by facilitating THEMIS-mediated inactivation of SHP1.The Journal of experimental medicine · 2023Article
- THEMIS increases TCR signaling in CD4Science signaling · 2023Article
- Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders.Nature reviews. Drug discovery · 2023Review
- The Protective Role ofFoods (Basel, Switzerland) · 2023Article
- Treg-specific deletion of the phosphatase SHP-1 impairs control of inflammationFrontiers in immunology · 2023Article
- Concomitant deletion of Ptpn6 and Ptpn11 in T cells fails to improve anticancer responses.EMBO reports · 2022Article
- Protein phosphatases regulate the liver microenvironment in the development of hepatocellular carcinoma.Experimental & molecular medicine · 2022Review
- Negative times negative equals positive, THEMIS sets the rule on thymic selection and peripheral T cell responses.Biomedical journal · 2022Review
- Immune Checkpoint Receptors Signaling in T Cells.International journal of molecular sciences · 2022Review
- HIV-1 Vif suppresses antiviral immunity by targeting STING.Cellular & molecular immunology · 2022Article
- T Cells With ActivatedFrontiers in immunology · 2022Article
- Two DuplicatedFrontiers in immunology · 2021Article
- PTPN2 Deficiency Enhances Programmed T Cell Expansion and Survival Capacity of Activated T Cells.Cell reports · 2020Article
- Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
Abstract
The protein-tyrosine phosphatase Shp1 is expressed ubiquitously in hematopoietic cells and is generally viewed as a negative regulatory molecule. Mutations in Ptpn6, which encodes Shp1, result in widespread inflammation and premature death, known as the motheaten (me) phenotype. Previous studies identified Shp1 as a negative regulator of TCR signaling, but the severe systemic inflammation in me mice may have confounded our understanding of Shp1 function in T cell biology. To define the T cell–intrinsic role of Shp1, we characterized mice with a T cell–specific Shp1 deletion (Shp1fl/fl CD4-cre). Surprisingly, thymocyte selection and peripheral TCR sensitivity were unaltered in the absence of Shp1. Instead, Shp1(fl/fl) CD4-cre mice had increased frequencies of memory phenotype T cells that expressed elevated levels of CD44. Activation of Shp1-deficient CD4⁺ T cells also resulted in skewing to the Th2 lineage and increased IL-4 production. After IL-4 stimulation of Shp1- deficient T cells, Stat 6 activation was sustained, leading to enhanced Th2 skewing. Accordingly, we observed elevated serum IgE in the steady state. Blocking or genetic deletion of IL-4 in the absence of Shp1 resulted in a marked reduction of the CD44hi population. Therefore, Shp1 is an essential negative regulator of IL-4 signaling in T lymphocytes.
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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.