Human airway mast cells proliferate and acquire distinct inflammation-driven phenotypes during type 2 inflammation.
Human airway mast cells proliferate and acquire distinct inflammation-driven phenotypes during type 2 inflammation.
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DOI：
10.1126/sciimmunol.abb7221
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发表时间：
2021-02-26
影响因子：
24.8
通讯作者：
Boyce JA
中科院分区：
文献类型：
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作者：
Dwyer DF;Ordovas-Montanes J;Allon SJ;Buchheit KM;Vukovic M;Derakhshan T;Feng C;Lai J;Hughes TK;Nyquist SK;Giannetti MP;Berger B;Bhattacharyya N;Roditi RE;Katz HR;Nawijn MC;Berg M;van den Berge M;Laidlaw TM;Shalek AK;Barrett NA;Boyce JA
肥大细胞（MC）在气道的2型（T2）过敏性炎症性疾病（包括哮喘和慢性鼻窦炎伴鼻息肉病（CRSwNP））中发挥病理生物学作用。不同的MC亚群浸润T2疾病的气道粘膜，包括上皮下MC表达蛋白酶类胰蛋白酶和糜蛋白酶（MCTC）和上皮MC表达类胰蛋白酶无糜蛋白酶（MCT）。然而，MC扩张的机制和其异质性的转录程序的基础是知之甚少。在这里，我们使用流式细胞术和单细胞RNA测序（scRNA-seq）进行全面的分析人类MC增生CRSwNP，T2嘌呤介导的炎症性疾病。我们将离散的细胞表面表型与CRSwNP MCT和MCTC的不同转录组联系起来，这代表了鼻息肉MC转录梯度的极化末端。我们发现在T2炎症过程中，CD 38 highCD 117 highMCs的上皮下群体显著扩增。这些CD 38 highCD 117 high MC表现出相对于扩增的MCT和MCTC亚群的中间表型。CD 38 highCD 117 high MC与循环MC祖细胞不同，并富集增殖，其在患有阿司匹林加重的呼吸道疾病（AERD）的CRSwNP患者中显著增加，AERD是一种以MC负荷增加和MC活化升高为特征的严重疾病亚组。我们观察到，在纤维化疾病和哮喘期间，在肺内也发现了表达息肉MCT样效应程序的MC，并进一步确定了鼻息肉和皮肤中MCTC之间的显著差异。这些结果表明，MC显示不同的炎症相关的效应程序，并建议在原位MC增殖是MC增生在人类T2炎症的主要组成部分。
Mast cells (MCs) play a pathobiologic role in type 2 (T2) allergic inflammatory diseases of the airway, including asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP). Distinct MC subsets infiltrate the airway mucosa in T2 disease, including subepithelial MCs expressing the proteases tryptase and chymase (MCTC) and epithelial MCs expressing tryptase without chymase (MCT). However, mechanisms underlying MC expansion and the transcriptional programs underlying their heterogeneity are poorly understood. Here we use flow cytometry and single-cell RNA-sequencing (scRNA-seq) to conduct a comprehensive analysis of human MC hyperplasia in CRSwNP, a T2 cytokine-mediated inflammatory disease. We link discrete cell surface phenotypes to the distinct transcriptomes of CRSwNP MCT and MCTC, which represent polarized ends of a transcriptional gradient of nasal polyp MCs. We discover a subepithelial population of CD38highCD117high MCs that is markedly expanded during T2 inflammation. These CD38highCD117high MCs exhibit an intermediate phenotype relative to the expanded MCT and MCTC subsets. CD38highCD117high MCs are distinct from circulating MC progenitors and are enriched for proliferation, which is markedly increased in CRSwNP patients with aspirin-exacerbated respiratory disease (AERD), a severe disease subset characterized by increased MC burden and elevated MC activation. We observe that MCs expressing a polyp MCT-like effector program are also found within the lung during fibrotic diseases and asthma, and further identify marked differences between MCTC in nasal polyps and skin. These results indicate that MCs display distinct inflammation-associated effector programs and suggest in situ MC proliferation is a major component of MC hyperplasia in human T2 inflammation.
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影响因子：
64.8
作者：
CEPEK, KL;SHAW, SK;BRENNER, MB
通讯作者：
BRENNER, MB
影响因子：
14.2
作者：
Abonia, J. Pablo;Blanchard, Carine;Butz, Bridget Buckmeier;Rainey, Heather F.;Collins, Margaret H.;Stringer, Keith;Putnam, Philip E.;Rothenberg, Marc E.
通讯作者：
Rothenberg, Marc E.
伊马替尼在严重难治性哮喘患者中抑制试剂盒。
DOI：
10.1056/nejmoa1613125
发表时间：
2017-05-18
期刊：
The New England journal of medicine
影响因子：
--
作者：
Cahill KN;Katz HR;Cui J;Lai J;Kazani S;Crosby-Thompson A;Garofalo D;Castro M;Jarjour N;DiMango E;Erzurum S;Trevor JL;Shenoy K;Chinchilli VM;Wechsler ME;Laidlaw TM;Boyce JA;Israel E
通讯作者：
Israel E
影响因子：
14.2
作者：
Dougherty, Ryan H.;Sidhu, Sukhvinder S.;Raman, Kavita;Solon, Margaret;Solberg, Owen D.;Caughey, George H.;Woodruff, Prescott G.;Fahy, John V.
通讯作者：
Fahy, John V.
影响因子：
30.5
作者：
通讯作者：
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