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Characterization of CD28null T cells in idiopathic pulmonary fibrosis.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2019-Jan-01 , DOI: 10.1038/s41385-018-0082-8
David M Habiel 1 , Milena S Espindola 1 , Chris Kitson 2 , Anthony V Azzara 2 , Ana Lucia Coelho 1 , Barry Stripp 1 , Cory M Hogaboam 1
Affiliation  

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease, with unknown etiopathogenesis and suboptimal therapeutic options. Previous reports have shown that increased T-cell numbers and CD28null phenotype is predictive of prognosis in IPF, suggesting that these cells might have a role in this disease. Flow cytometric analysis of explanted lung cellular suspensions showed a significant increase in CD8+ CD28null T cells in IPF relative to normal lung explants. Transcriptomic analysis of CD3+ T cells isolated from IPF lung explants revealed a loss of CD28-transcript expression and elevation of pro-inflammatory cytokine expression in IPF relative to normal T cells. IPF lung explant-derived T cells (enriched with CD28null T cells), but not normal donor lung CD28+ T cells induced dexamethasone-resistant lung remodeling in humanized NSG mice. Finally, CD28null T cells expressed similar CTLA4 and significantly higher levels of PD-1 proteins relative to CD28+ T cells and blockade of either proteins in humanized NSG mice, using anti-CTLA4, or anti-PD1, mAb treatment-accelerated lung fibrosis. Together, these results demonstrate that IPF CD28null T cells may promote lung fibrosis but the immune checkpoint proteins, CTLA-4 and PD-1, appears to limit this effect.

中文翻译:


CD28null T 细胞在特发性肺纤维化中的特征。



特发性肺纤维化(IPF)是一种纤维化性肺部疾病,其发病机制尚不清楚,治疗方案也欠佳。之前的报告表明,T 细胞数量的增加和 CD28缺失表型可以预测 IPF 的预后,表明这些细胞可能在这种疾病中发挥作用。外植肺细胞悬液的流式细胞分析显示,与正常肺外植体相比,IPF 中 CD8 + CD28 null T 细胞显着增加。对从 IPF 肺外植体中分离的 CD3 + T 细胞进行转录组分析显示,与正常 T 细胞相比,IPF 中 CD28 转录物表达缺失,促炎细胞因子表达升高。 IPF 肺外植体衍生的 T 细胞(富含 CD28 null T 细胞)而非正常供体肺 CD28 + T 细胞在人源化 NSG 小鼠中诱导地塞米松耐药性肺重塑。最后,与 CD28 + T 细胞相比,CD28 null T 细胞表达相似的 CTLA4,且 PD-1 蛋白水平显着更高,并且使用抗 CTLA4 或抗 PD1 mAb 治疗加速肺纤维化,在人源化 NSG 小鼠中阻断任一蛋白。总之,这些结果表明 IPF CD28 null T 细胞可能促进肺纤维化,但免疫检查点蛋白 CTLA-4 和 PD-1 似乎限制了这种效应。
更新日期:2019-01-26
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