The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF).
The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF).
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特发性肺纤维化（IPF）从正常肺解剖结构转变为最小和已确定的纤维化。
DOI：
10.1016/j.ebiom.2021.103325
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发表时间：
2021-04
期刊：
影响因子：
11.1
通讯作者：
Hogg JC
中科院分区：
文献类型：
--
作者：
Xu F;Tanabe N;Vasilescu DM;McDonough JE;Coxson HO;Ikezoe K;Kinose D;Ng KW;Verleden SE;Wuyts WA;Vanaudenaerde BM;Verschakelen J;Cooper JD;Lenburg ME;Morshead KB;Abbas AR;Arron JR;Spira A;Hackett TL;Colby TV;Ryerson CJ;Ng RT;Hogg JC
特发性肺纤维化(IPF)的一个重要病理特征是从正常肺解剖到微小的、已建立的纤维化的转变。这份报告的目的是研究与这种转变相关的分子和细胞机制。对重度IPF患者(n=9)进行术前多层螺旋CT(MDCT)扫描，以确定轻度纤维化(n=27)和已建立纤维化(n=27)。采用MDCT、Micro-CT、定量组织学和下一代测序技术对24例来自供者对照(n=4)的样本与最小和已建立的纤维化样本进行比较。目前的结果扩展了早期关于从正常肺解剖到微小和已建立的纤维化的报道，表明与对照组相比，TGFBI和T细胞共刺激基因被激活，抑制性免疫检查点基因下调。这些基因的表达模式表明激活了现场免疫反应，这进一步得到了以能够形成淋巴滤泡的淋巴细胞为主的炎性免疫细胞的增加的支持。此外，纤维化途径、粘蛋白分泌、表面活性物质、TLRs和细胞因子风暴相关基因也参与了从正常肺解剖到轻微和已建立的纤维化的转变。从正常肺解剖到轻微和已建立的纤维化的转变与参与组织修复过程的基因、免疫反应的激活以及CD4、CD8、B细胞和巨噬细胞的增加有关。这些分子和细胞事件与IPF结构异常的发生发展有关，可能参与了IPF的发病机制。
The transition from normal lung anatomy to minimal and established fibrosis is an important feature of the pathology of idiopathic pulmonary fibrosis (IPF). The purpose of this report is to examine the molecular and cellular mechanisms associated with this transition. Pre-operative thoracic Multidetector Computed Tomography (MDCT) scans of patients with severe IPF (n = 9) were used to identify regions of minimal(n = 27) and established fibrosis(n = 27). MDCT, Micro-CT, quantitative histology, and next-generation sequencing were used to compare 24 samples from donor controls (n = 4) to minimal and established fibrosis samples. The present results extended earlier reports about the transition from normal lung anatomy to minimal and established fibrosis by showing that there are activations of TGFBI, T cell co-stimulatory genes, and the down-regulation of inhibitory immune-checkpoint genes compared to controls. The expression patterns of these genes indicated activation of a field immune response, which is further supported by the increased infiltration of inflammatory immune cells dominated by lymphocytes that are capable of forming lymphoid follicles. Moreover, fibrosis pathways, mucin secretion, surfactant, TLRs, and cytokine storm-related genes also participate in the transitions from normal lung anatomy to minimal and established fibrosis. The transition from normal lung anatomy to minimal and established fibrosis is associated with genes that are involved in the tissue repair processes, the activation of immune responses as well as the increased infiltration of CD4, CD8, B cell lymphocytes, and macrophages. These molecular and cellular events correlate with the development of structural abnormality of IPF and probably contribute to its pathogenesis.
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影响因子：
29.7
作者：
Davis BK;Wen H;Ting JP
通讯作者：
Ting JP
影响因子：
7.3
作者：
Adegunsoye A;Hrusch CL;Bonham CA;Jaffery MR;Blaine KM;Sullivan M;Churpek MM;Strek ME;Noth I;Sperling AI
通讯作者：
Sperling AI
DOI：
10.1038/nri.2016.117
发表时间：
2017-01
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Iwasaki A;Foxman EF;Molony RD
通讯作者：
Molony RD
DOI：
10.1056/nejmoa1801562
发表时间：
2018-12-06
期刊：
The New England journal of medicine
影响因子：
--
作者：
Juge PA;Lee JS;Ebstein E;Furukawa H;Dobrinskikh E;Gazal S;Kannengiesser C;Ottaviani S;Oka S;Tohma S;Tsuchiya N;Rojas-Serrano J;González-Pérez MI;Mejía M;Buendía-Roldán I;Falfán-Valencia R;Ambrocio-Ortiz E;Manali E;Papiris SA;Karageorgas T;Boumpas D;Antoniou K;van Moorsel CHM;van der Vis J;de Man YA;Grutters JC;Wang Y;Borie R;Wemeau-Stervinou L;Wallaert B;Flipo RM;Nunes H;Valeyre D;Saidenberg-Kermanac'h N;Boissier MC;Marchand-Adam S;Frazier A;Richette P;Allanore Y;Sibilia J;Dromer C;Richez C;Schaeverbeke T;Lioté H;Thabut G;Nathan N;Amselem S;Soubrier M;Cottin V;Clément A;Deane K;Walts AD;Fingerlin T;Fischer A;Ryu JH;Matteson EL;Niewold TB;Assayag D;Gross A;Wolters P;Schwarz MI;Holers M;Solomon JJ;Doyle T;Rosas IO;Blauwendraat C;Nalls MA;Debray MP;Boileau C;Crestani B;Schwartz DA;Dieudé P
通讯作者：
Dieudé P
影响因子：
3.7
作者：
Seibold MA;Smith RW;Urbanek C;Groshong SD;Cosgrove GP;Brown KK;Schwarz MI;Schwartz DA;Reynolds SD
通讯作者：
Reynolds SD