NPJ autoimmunity最新文献

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Type 1 diabetes SIRPG risk variants increase SIRPγ expression and CD47 loss enhances CD8+ T cell cytotoxicity. 1型糖尿病SIRPG风险变异增加SIRPγ表达,CD47缺失增强CD8+ T细胞毒性。
NPJ autoimmunity Pub Date : 2026-01-01 Epub Date: 2026-10-01 DOI: 10.1038/s44483-026-00002-5
Robert C Sharp, Matthew E Brown, Leeana D Peters, Rhonda Bacher, Laura M Jacobsen, Todd M Brusko
{"title":"Type 1 diabetes <i>SIRPG</i> risk variants increase SIRP<i>γ</i> expression and CD47 loss enhances CD8<sup>+</sup> T cell cytotoxicity.","authors":"Robert C Sharp, Matthew E Brown, Leeana D Peters, Rhonda Bacher, Laura M Jacobsen, Todd M Brusko","doi":"10.1038/s44483-026-00002-5","DOIUrl":"https://doi.org/10.1038/s44483-026-00002-5","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) risk variants within <i>SIRPG</i> influence transcript splicing and alter the expression of signal regulatory protein gamma (SIRPγ) on human T cells; however, the functional consequences of the risk variants remain poorly defined. Here, we demonstrate that peripheral blood mononuclear cells from individuals carrying a T1D-associated risk haplotype exhibit increased membrane-bound SIRPγ and reduced expression of its ligand CD47 across CD4<sup>+</sup> and CD8<sup>+</sup> T cell subsets compared to a protective haplotype. To interrogate the impact of impaired CD47 signaling, we generated CRISPR/Cas9 knockout (KO) models in Jurkat and primary human CD8<sup>+</sup> T cells, as well as a pancreatic β-cell line (βLox5). <i>CD47</i>-deficient T cells displayed heightened activation, reduced co-inhibitory receptor expression, and increased production of IL-2 and TNF following stimulation. Furthermore, <i>CD47</i> KO CD8<sup>+</sup> T cell avatars expressing an HLA-A*02:01-restricted, IGRP<sub>265-273</sub>-reactive T cell receptor (TCR) exhibited enhanced cytotoxicity toward βLox5 targets, while <i>CD47</i> KO βLox5 cells were more susceptible to apoptosis. These findings reveal that CD47 signaling constrains T cell effector function and β-cell susceptibility, and its disruption through altered SIRPγ-ligation may contribute to autoimmune pathogenesis in T1D.</p>","PeriodicalId":524223,"journal":{"name":"NPJ autoimmunity","volume":"1 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149123886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neurotransmitters as regulators of autoimmunity: mechanisms and translational targeting. 神经递质作为自身免疫的调节剂:机制和翻译靶向。
NPJ autoimmunity Pub Date : 2026-01-01 Epub Date: 2026-09-10 DOI: 10.1038/s44483-026-00001-6
Taruna Lamba, George C Tsokos
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引用次数: 0
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