ArticleJournal of immunology (Baltimore, Md. : 1950)2011
SLAP deficiency enhances number and function of regulatory T cells preventing chronic autoimmune arthritis in SKG mice.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- ZAP-70 in Signaling, Biology, and Disease.Annual review of immunology · 2018Review
- Loss of the Protein Tyrosine Phosphatase PTPN22 Reduces Mannan-Induced Autoimmune Arthritis in SKG Mice.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Quantitative reduction of the TCR adapter protein SLP-76 unbalances immunity and immune regulation.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Thymic Nurse Cells Participate in Heterotypic Internalization and Repertoire Selection of Immature Thymocytes; Their Removal from the Thymus of Autoimmune Animals May be Important to Disease Etiology.Current molecular medicine · 2015Review
- The Emerging and Diverse Roles of Src-Like Adaptor Proteins in Health and Disease.Mediators of inflammation · 2015Review
- SLAP deficiency decreases dsDNA autoantibody production.Clinical immunology (Orlando, Fla.) · 2014Article
- Regulation of T cell receptor complex-mediated signaling by ubiquitin and ubiquitin-like modifications.American journal of clinical and experimental immunology · 2014Review
- SLAP deficiency increases TCR avidity leading to altered repertoire and negative selection of cognate antigen-specific CD8+ T cells.Immunologic research · 2013Article
- The discovery of a reciprocal relationship between tyrosine-kinase signaling and cullin neddylation.PloS one · 2013Article
- Pregnancy amelioration of arthritis in SKG mice corresponds with alterations in serum amyloid A3 levels.American journal of clinical and experimental immunology · 2012Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
To test if manipulating TCR complex-mediated signaling (TCR signaling) could treat autoimmune disease, we generated the double SKG Src-like adapter protein (SLAP) knockout (DSSKO) mouse model. The SKG mutation in ZAP70 and SLAP have opposing functions on the regulation of TCR signaling. The combination of these two mutations alters TCR signaling in the context of a defined genetic background, uniform environmental conditions, and a well-characterized signaling disruption. In contrast to SKG mice, DSSKO mice do not develop zymosan-induced chronic autoimmune arthritis. This arthritis prevention is not due to significant alterations in thymocyte development or repertoire selection but instead enhanced numbers of regulatory T cells (Tregs) and decreased numbers of Th17 cells skewing the ratio of Tregs to autoreactive effector T cells. Treg depletion and/or functional blockade led to the development of arthritis in DSSKO mice. In vitro suppression of effector T cell proliferation was also enhanced, demonstrating that DSSKO mice have increased numbers of Tregs with increased function. Understanding how TCR signals influence development, expansion, and function of Tregs in DSSKO mice could advance our ability to manipulate Treg biology to treat ultimately autoimmune disease.
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Registered trials
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