Rationale: Fibrotic hypersensitivity pneumonitis is a debilitating interstitial lung disease driven by incompletely understood immune mechanisms. Objectives: To elucidate immune aberrations in fibrotic hypersensitivity pneumonitis in single-cell resolution. Methods: Single-cell 5' RNA sequencing was conducted on peripheral blood mononuclear cells and bronchoalveolar lavage cells obtained from 45 patients with fibrotic hypersensitivity pneumonitis, 63 idiopathic pulmonary fibrosis, 4 non-fibrotic hypersensitivity pneumonitis, and 36 healthy controls in the United States and Mexico. Analyses included differential gene expression (Seurat), transcription factor activity imputation (DoRothEA-VIPER), and trajectory analyses (Monocle3/Velocyto-scVelo-CellRank). Measurements and Main Results: Overall, 501,534 peripheral blood mononuclear cells from 110 patients and controls and 88,336 bronchoalveolar lavage cells from 19 patients were profiled. Compared to controls, fibrotic hypersensitivity pneumonitis has elevated classical monocytes (adjusted-p=2.5e-3) and are enriched in CCL3hi/CCL4hi and S100Ahi classical monocytes (adjusted-p<2.2e-16). Trajectory analyses demonstrate that S100Ahi classical monocytes differentiate into SPP1hi lung macrophages associated with fibrosis. Compared to both controls and idiopathic pulmonary fibrosis, fibrotic hypersensitivity pneumonitis patient cells are significantly enriched in GZMhi cytotoxic T cells. These cells exhibit transcription factor activities indicative of TGFβ and TNFα/NFκB pathways. These results are publicly available at https://ildimmunecellatlas.org. Conclusions: Single-cell transcriptomics of fibrotic hypersensitivity pneumonitis patients uncovered novel immune perturbations, including previously undescribed increases in GZMhi cytotoxic CD4+ and CD8+ T cells - reflecting this disease's unique inflammatory T-cell driven nature - as well as increased S100Ahi and CCL3hi/CCL4hi classical monocytes also observed in idiopathic pulmonary fibrosis. Both cell populations may guide the development of new biomarkers and therapeutic interventions.

Amy Y Zhao

Avraham Unterman

Nebal S. Abu Hussein

Prapti Sharma

Fadi Nekola

Jasper Flint

Xiting Yan

Taylor S Adams

Aurelien Justet

Tomokazu S. Sumida

Jiayi Zhao

Jonas C. Schupp

Micha Sam B. Raredon

Farida Ahangari

Giuseppe Deluliis

Yingze Zhang

Ivette Buendia-Roldan

Ayodeji Adegunsoye

Anne I. Sperling

Antje Prasse

Changwan Ryu

Erica Herzog

Moises Selman

Annie Pardo

Naftali Kaminski

American Journal of Respiratory and Critical Care Medicine

《美国呼吸与重症监护医学杂志》专注于人类生物学和疾病，以及有助于了解影响呼吸系统和危重病人的疾病的病理生理学和治疗的动物和体外研究。主要以细胞和分子生物学为基础的论文发表在配套期刊《美国呼吸细胞和分子生物学杂志》上。该杂志还寻求以多种形式发表有关感兴趣领域的临床试验和优秀评论文章。最先进的评论是一篇论文，通常涵盖一个广泛的领域，将基准研究带到床边。较短的评论以重症监护观点或肺部观点发表。这些通常集中在更有限的领域，并就特定过程的护理提出一致意见。简明临床评论提供了基于证据的文献综合，这些文献涉及对肺、重症监护和睡眠医学实践具有根本重要性的主题。为该领域提供进步或不寻常贡献的图像以“肺、重症监护、睡眠医学和科学中的图像”的形式发布。

The American Journal of Respiratory and Critical Care Medicine focuses on human biology and diseases, as well as animal and in vitro studies that help understand the pathophysiology and treatment of diseases affecting the respiratory system and critically ill patients. Papers primarily based on cellular and molecular biology are published in the companion journal, the American Journal of Respiratory Cell and Molecular Biology. The journal also seeks to publish clinical trials and outstanding review articles in various formats related to areas of interest. State-of-the-art reviews are comprehensive papers that cover a broad field, bridging foundational research to bedside applications. Shorter reviews are published from the perspectives of critical care or pulmonary medicine, focusing on more limited areas and providing consensus on the care of specific processes. Concise clinical reviews offer evidence-based literature syntheses on topics of fundamental importance to pulmonary, critical care, and sleep medicine practice. Images that provide advances or unusual contributions to the field are published in the form of 'Images in Lung, Critical Care, Sleep Medicine, and Science.'

《美国呼吸与重症监护医学杂志》专注于人类生物学和疾病，以及有助于理解影响呼吸系统和危重病患者的疾病的病理生理学和治疗的动物及体外研究。主要以细胞和分子生物学为基础的论文会发表在配套期刊《美国呼吸细胞和分子生物学杂志》上。该杂志还欢迎以多种形式发表有关感兴趣领域的临床试验和优秀评论文章。最先进的评论通常涵盖广泛的领域，将基准研究与临床实践相结合。较短的评论则从重症监护或肺部的角度出发，集中在更具体的领域，并就特定过程的护理提出一致意见。简明临床评论提供基于证据的文献综述，涉及对肺、重症监护和睡眠医学实践至关重要的主题。此外，提供该领域进展或不寻常贡献的图像将以“肺、重症监护、睡眠医学和科学中的图像”的形式发布。

Am J Respir Crit Care Med

Single Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis

单细胞分析揭示纤维化性过敏性肺炎中的新型免疫干扰

Category	Quartile
医学	1
医学, 危重病医学	1
医学, 呼吸系统	1

Single Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis

ivySCI AI Smartly Parses PDF, Answers Researchers' Questions, and Helps You Understand Papers in Seconds

Journal Info

Category	Quartile
RESPIRATORY SYSTEM	1