CAGE sequencing reveals CFTR-dependent dysregulation of type I IFN signaling in activated cystic fibrosis macrophages.
CAGE sequencing reveals CFTR-dependent dysregulation of type I IFN signaling in activated cystic fibrosis macrophages.
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CAGE测序揭示了活化囊性纤维化巨噬细胞中cftr依赖性I型IFN信号失调。
DOI：
10.1126/sciadv.adg5128
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发表时间：
2023-05-26
期刊：
影响因子：
13.6
通讯作者：
Gray RD
中科院分区：
文献类型：
--
作者：
Gillan JL;Chokshi M;Hardisty GR;Clohisey Hendry S;Prasca-Chamorro D;Robinson NJ;Lasota B;Clark R;Murphy L;Whyte MKB;Baillie JK;Davidson DJ;Bao G;Gray RD
An intense, nonresolving airway inflammatory response leads to destructive lung disease in cystic fibrosis (CF). Dysregulation of macrophage immune function may be a key facet governing the progression of CF lung disease, but the underlying mechanisms are not fully understood. We used 5′ end centered transcriptome sequencing to profile P. aeruginosa LPS-activated human CF macrophages, showing that CF and non-CF macrophages deploy substantially distinct transcriptional programs at baseline and following activation. This includes a significantly blunted type I IFN signaling response in activated patient cells relative to healthy controls that was reversible upon in vitro treatment with CFTR modulators in patient cells and by CRISPR-Cas9 gene editing to correct the F508del mutation in patient-derived iPSC macrophages. These findings illustrate a previously unidentified immune defect in human CF macrophages that is CFTR dependent and reversible with CFTR modulators, thus providing new avenues in the search for effective anti-inflammatory interventions in CF. Macrophages in Cystic Fibrosis exhibit intrinsic, CFTR-dependent, dysregulated type I IFN signalling following activation.
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DOI：
10.1038/mtna.2014.64
发表时间：
2014-12-02
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.3
作者：
Bruscia EM;Bonfield TL
通讯作者：
Bonfield TL
DOI：
10.4049/jimmunol.1300221
发表时间：
2013-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bessich JL;Nymon AB;Moulton LA;Dorman D;Ashare A
通讯作者：
Ashare A
影响因子：
4.6
作者：
Alasoo K;Martinez FO;Hale C;Gordon S;Powrie F;Dougan G;Mukhopadhyay S;Gaffney DJ
通讯作者：
Gaffney DJ
影响因子：
3.7
作者：
del Campo R;Martínez E;del Fresno C;Alenda R;Gómez-Piña V;Fernández-Ruíz I;Siliceo M;Jurado T;Toledano V;Arnalich F;García-Río F;López-Collazo E
通讯作者：
López-Collazo E