The Immunome in Two Inherited Forms of Pulmonary Fibrosis.
The Immunome in Two Inherited Forms of Pulmonary Fibrosis.
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DOI：
10.3389/fimmu.2018.00076
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发表时间：
2018
影响因子：
7.3
通讯作者：
Gochuico BR
中科院分区：
文献类型：
--
作者：
El-Chemaly S;Cheung F;Kotliarov Y;O'Brien KJ;Gahl WA;Chen J;Perl SY;Biancotto A;Gochuico BR
肺纤维化中的免疫组学（免疫细胞表型、基因表达和血清细胞因子谱）尚不完全明确。对遗传性肺纤维化的研究提供了对一般纤维化肺病机制的见解。为了明确外周血细胞和分子免疫表型，我们对一组有家族性肺纤维化（FPF）、Hermansky-Pudlak综合征肺纤维化（HPSPF）、慢性肺纤维化（COPD）和慢性肺纤维化（COPD）的患者进行了外周血单个核细胞的高维流式细胞术和大规模基因表达以及血清蛋白质组学多重分析，并进行了比较。和他们未受影响的亲戚。我们的研究结果显示FPF患者外周血中激活的中枢记忆辅助细胞浓度较高。在家族性或HPSPF患者中，CD 38+记忆CD 27 − B细胞、伊加+记忆CD 27 + B细胞、IgM+和IgD+ B细胞以及CD 39 + T辅助细胞的比例增加，而CD 39 − T辅助细胞的比例减少。基因表达和血清蛋白质组学分析显示，在循环单核细胞中与有丝分裂和细胞周期控制相关的上调基因的富集以及几种分析物（包括瘦素、细胞因子和生长因子）水平的改变。总之，肺外免疫组失调是FPF或HPSPF的表型特征。研究血液免疫组的进一步研究表明，以确定免疫系统失调在肺纤维化发病机制中的作用。，标识符NCT 00968084、NCT 01200823、NCT 00001456和NCT 00084305。
The immunome (immune cell phenotype, gene expression, and serum cytokines profiling) in pulmonary fibrosis is incompletely defined. Studies focusing on inherited forms of pulmonary fibrosis provide insights into mechanisms of fibrotic lung disease in general. To define the cellular and molecular immunologic phenotype in peripheral blood, high-dimensional flow cytometry and large-scale gene expression of peripheral blood mononuclear cells and serum proteomic multiplex analyses were performed and compared in a cohort with familial pulmonary fibrosis (FPF), an autosomal dominant disorder with incomplete penetrance; Hermansky–Pudlak syndrome pulmonary fibrosis (HPSPF), a rare autosomal recessive disorder; and their unaffected relatives. Our results showed high peripheral blood concentrations of activated central memory helper cells in patients with FPF. Proportions of CD38+ memory CD27− B-cells, IgA+ memory CD27+ B-cells, IgM+ and IgD+ B-cells, and CD39+ T helper cells were increased whereas those of CD39− T helper cells were reduced in patients affected with either familial or HPSPF. Gene expression and serum proteomic analyses revealed enrichment of upregulated genes associated with mitosis and cell cycle control in circulating mononuclear cells as well as altered levels of several analytes, including leptin, cytokines, and growth factors. In conclusion, dysregulation of the extra-pulmonary immunome is a phenotypic feature of FPF or HPSPF. Further studies investigating the blood immunome are indicated to determine the role of immune system dysregulation in the pathogenesis of pulmonary fibrosis. , identifiers NCT00968084, NCT01200823, NCT00001456, and NCT00084305.