Phospholipase Cγ1 is essential for T cell development, activation, and tolerance
Open accessAbstract
Phospholipase Cγ1 (PLCγ1) is an important signaling effector of T cell receptor (TCR). To investigate the role of PLCγ1 in T cell biology, we generated and examined mice with T cell–specific deletion of PLCγ1. We demonstrate that PLCγ1 deficiency affects positive and negative selection, significantly reduces single-positive thymocytes and peripheral T cells, and impairs TCR-induced proliferation and cytokine production, and the activation of ERK, JNK, AP-1, NFAT, and NF-κB. Importantly, PLCγ1 deficiency impairs the development and function of FoxP3+ regulatory T cells, causing inflammatory/autoimmune symptoms. Therefore, PLCγ1 is essential for T cell development, activation, and tolerance.
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In the absence of PLCγ2, T cell development and TCR-mediated proliferation are normal, with development instead depending on PLCγ1.
“Inducible KO mice showed T cell development and T cell receptor (TCR)-mediated proliferation were normal in the absence of PLCγ2 (24, 26), with development instead depending on the closely related family member PLCγ1 (60).”
From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [60]
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- Authors
- Fu, G., Chen, Y., Yu, M., Podd, A., Schuman, J., He, Y., Di, L., Yassai, M., Haribhai, D., North, P. E., Gorski, J., Williams, C. B., Wang, D., & Wen, R.
- Affiliations
- Versiti Blood Center of Wisconsin (US)
- The Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53226 1
- State Key Laboratory of Pharmaceutical Biotechnology (CN)
- Medical College of Wisconsin (US)
- Children's Hospital of Wisconsin (US)
- Corresponding author
- Wen, Renren
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2010-02-01
- Volume
- 207
- Issue
- 2
- Pages
- 309-318
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2822604
- OpenAlex
- W2071131149
- Cited by
- 133
- References
- 29
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 7 · 2023: 15 · 2022: 7 · 2021: 8 · 2020: 5 · 2019: 6 · 2018: 4 · 2017: 7 · 2016: 11 · 2015: 6 · 2014: 9 · 2013: 12 · 2012: 10
- FWCI
- 5.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ai085090-10)
- National Heart, Lung, and Blood Institute (R01HL073284)
- National Institute of Allergy and Infectious Diseases (R01-AI-085090, U19AI062627, R01AI079087, R01AI052327)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- phospholipase C-gamma1, T cell development, T cell activation, T cell tolerance, T cell receptor signaling, thymic selection, Foxp3+ regulatory T cells, autoimmunity, ERK, JNK, NFAT, NF-κB, AP-1, T cell-specific knockout mice
- MeSH terms
- Animals, Autoimmune Diseases, Cell Differentiation, Inflammation, Lymphocyte Activation, Mice, Transgenic, Receptors, Antigen, T-Cell, T-Lymphocytes, Autoimmunity, T-Lymphocyte Subsets, NF-kappa B, Transcription Factor AP-1, MAP Kinase Kinase 4, NFATC Transcription Factors, Mice, Forkhead Transcription Factors, Phospholipase C gamma
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