Autoimmunity-Associated LYP-W620 Does Not Impair Thymic Negative Selection of Autoreactive T Cells
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منابع مشابه
Autoimmunity-Associated LYP-W620 Does Not Impair Thymic Negative Selection of Autoreactive T Cells
A C1858T (R620W) variation in the PTPN22 gene encoding the tyrosine phosphatase LYP is a major risk factor for human autoimmunity. LYP is a known negative regulator of signaling through the T cell receptor (TCR), and murine Ptpn22 plays a role in thymic selection. However, the mechanism of action of the R620W variant in autoimmunity remains unclear. One model holds that LYP-W620 is a gain-of-fu...
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T cell-mediated autoimmune diseases such as type 1 diabetes (T1D) are believed to be the result in part of inefficient negative selection of self-specific thymocytes. However, the events regulating thymic negative selection are not fully understood. In the current study, we demonstrate that nonobese diabetic (NOD) mice lacking expression of the Mer tyrosine kinase (MerTK) have reduced inflammat...
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The Autoimmunity Risk Variant LYP-W620 Cooperates with CSK in the Regulation of TCR Signaling
The protein tyrosine phosphatase LYP, a key regulator of TCR signaling, presents a single nucleotide polymorphism, C1858T, associated with several autoimmune diseases such as type I diabetes, rheumatoid arthritis, and lupus. This polymorphism changes an R by a W in the P1 Pro rich motif of LYP, which binds to CSK SH3 domain, another negative regulator of TCR signaling. Based on the analysis of ...
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The thymus contains a population of B cells that colocalize with dendritic cells and medullary thymic epithelial cells in the thymic medulla. The development and functional significance of these cells are largely unknown. Using recombination-activating gene 2 GFP reporter mice along with parabiosis experiments, we demonstrate that the vast majority of thymic B cells develop from progenitors wit...
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ژورنال
عنوان ژورنال: PLoS ONE
سال: 2014
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0086677