Multiplatform Single-Cell Analysis Identifies Immune Cell Types Enhanced in Pulmonary Fibrosis

Serezani, Ana Paula Moreira; Pascoalino, Bruno D; Bazzano, Julia; Vowell, Katherine N.; Tanjore, Harikrishna; Taylor, Chase J.; Calvi, C.; Mccall, Scott A; Bacchetta, Matthew; Shaver, Ciara M.; Ware, Lorraine B.; Salisbury, M.L.; Banovich, Nicholas E.; Kendall, Peggy L.; Kropski, Jonathan A.; Blackwell, Timothy S.

doi:10.1165/rcmb.2021-0418oc

Cited by 36 publications

(34 citation statements)

References 82 publications

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“…Increasing evidences indicate that immune cells are linked to the development of IPF ( 1 , 19 , 41 , 42 ). Kreuter et al.…”

Section: Discussionmentioning

confidence: 99%

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Identification and validation of autophagy-related gene expression for predicting prognosis in patients with idiopathic pulmonary fibrosis

Huang

Xu²,

Chen³

et al. 2022

Front. Immunol.

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BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal fibrotic pulmonary disease with unknow etiology. Owing to lack of reliable prognostic biomarkers and effective treatment measures, patients with IPF usually exhibit poor prognosis. The aim of this study is to establish a risk score prognostic model for predicting the prognosis of patients with IPF based on autophagy-related genes.MethodsThe GSE70866 dataset was obtained from the gene expression omnibus (GEO) database. The autophagy-related genes were collected from the Molecular Signatures Database (MSigDB). Gene enrichment analysis for differentially expressed genes (DEGs) was performed to explore the function of DEGs. Univariate, least absolute shrinkage and selection operator (LASSO), as well as multivariate Cox regression analyses were conducted to identify a multi-gene prognostic model. Receiver operating characteristic (ROC) curve was applied to assess the prediction accuracy of the model. The expression of genes screened from the prognostic model was validated in clinical samples and human lung fibroblasts by qPCR and western blot assays.ResultsAmong the 514 autophagy-related genes, a total of 165 genes were identified as DEGs. These DEGs were enriched in autophagy-related processes and pathways. Based on the univariate, LASSO, and multivariate Cox regression analyses, two genes (MET and SH3BP4) were included for establishing the risk score prognostic model. According to the median value of the risk score, patients with IPF were stratified into high-risk and low-risk groups. Patients in high-risk group had shorter overall survival (OS) than low-risk group in both training and test cohorts. Multivariate regression analysis indicated that prognostic model can act as an independent prognostic indicator for IPF. ROC curve analysis confirmed the reliable predictive value of prognostic model. In the validation experiments, upregulated MET expression and downregulated SH3BP4 expression were observed in IPF lung tissues and TGF-β1-activated human lung fibroblasts, which is consistent with results from microarray data analysis.ConclusionThese findings indicated that the risk score prognostic model based on two autophagy-related genes can effectively predict the prognosis of patients with IPF.

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“…Increasing evidences indicate that immune cells are linked to the development of IPF ( 1 , 19 , 41 , 42 ). Kreuter et al.…”

Section: Discussionmentioning

confidence: 99%

“…Increasing evidences indicate that immune cells are linked to the development of IPF (1,19,41,42). Kreuter et al reported that increased monocyte count was related to elevated risks of IPF progression, hospitalization and mortality for patients with IPF (43).…”

Section: A B Cmentioning

confidence: 99%

Identification and validation of autophagy-related gene expression for predicting prognosis in patients with idiopathic pulmonary fibrosis

Huang

Xu²,

Chen³

et al. 2022

Front. Immunol.

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“…Cluster #5508 was prevalent in sarcoidosis and characterized by CD4 + CD226 + CXCR3 + . Cluster #5520, which was prevalent in IPF, was comprised of CD4 + IL-2R + TIGIT + LAG3 + , considered as CD4 + regulatory T cells (Tregs) (6). Cluster #5527, which was abundant in CTD-ILDs, was marked by CD8 + CD57 + PD-1 + TIGIT + .…”

Section: Characteristic T Cell Subpopulations In the Lungs Of Ildsmentioning

confidence: 99%

“…Recent studies have showed that the existence of a unique population of macrophages in IPF lung explants (10) (11) (12) and murine models of pulmonary fibrosis (13) (14). T cells have also been implicated in the development of ILDs (6) (15).…”

Section: Introductionmentioning

confidence: 99%

Mass cytometry identifies characteristic immune cell subsets in bronchoalveolar lavage fluid from interstitial lung diseases

Hata

Yanagihara

Matsubara

et al. 2023

Preprint

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Immune cells have been implicated in interstitial lung diseases (ILDs), although their phenotypes and effector mechanisms remain poorly understood. To better understand these cells, we conducted an exploratory mass cytometry analysis of immune cell subsets in bronchoalveolar lavage fluid (BALF) from patients with idiopathic pulmonary fibrosis (IPF), connective-tissue disease (CTD)-related ILD, and sarcoidosis, using two panels including 64 markers. Among myeloid cells, we observed the expansion of CD14+CD36hiCD84himonocyte populations in IPF. These CD14+CD36hiCD84hisubsets were also increased in ILDs with a progressive phenotype, particularly in a case of acute exacerbation (AEx) of IPF. Analysis of B cells revealed the presence of cells at various stages of differentiation in BALF, with a higher percentage of IgG memory B cells in CTD-ILDs and a trend toward more FCRL5+B cells. These FCRL5+B cells were also present in the patient with AEx-IPF and sarcoidosis with advanced lung lesions. Among T cells, we found increased levels of IL-2R+TIGIT+LAG3+CD4+T cells in IPF, increased levels of CXCR3+CD226+CD4+T cells in sarcoidosis, and increased levels of PD1+TIGIT+CD57+CD8+T cells in CTD-ILDs. Together, these findings underscore the diverse immunopathogenesis of ILDs.

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“…Furthermore, activated macrophages produce ferritin, which is a significant prognostic factor of AE-IPF [ 44 ]. In the chronic stage of IPF, single-cell RNA-sequencing revealed an increased number of alveolar macrophages, dendritic cells (DC), and memory T-cells in the fibrotic lung [ 45 ]. In collaboration with profibrotic/M2 macrophages, CD4+helper T (Th)-cells such as Th2, Th17, and regulatory T-cell (Tregs) facilitate the profibrotic process [ 46 ].…”

Section: Acute Exacerbation Of Ipfmentioning

confidence: 99%

Pathological Roles of Pulmonary Cells in Acute Lung Injury: Lessons from Clinical Practice

Enomoto

2022

IJMS

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Interstitial lung diseases (ILD) are relatively rare and sometimes become life threatening. In particular, rapidly progressive ILD, which frequently presents as acute lung injury (ALI) on lung histopathology, shows poor prognosis if proper and immediate treatments are not initiated. These devastating conditions include acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), clinically amyopathic dermatomyositis (CADM), epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-induced lung injury, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection named coronavirus disease 2019 (COVID-19). In this review, clinical information, physical findings, laboratory examinations, and findings on lung high-resolution computed tomography and lung histopathology are presented, focusing on majorly damaged cells in each disease. Furthermore, treatments that should be immediately initiated in clinical practice for each disease are illustrated to save patients with these diseases.

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Multiplatform Single-Cell Analysis Identifies Immune Cell Types Enhanced in Pulmonary Fibrosis

Cited by 36 publications

References 82 publications

Identification and validation of autophagy-related gene expression for predicting prognosis in patients with idiopathic pulmonary fibrosis

Identification and validation of autophagy-related gene expression for predicting prognosis in patients with idiopathic pulmonary fibrosis

Mass cytometry identifies characteristic immune cell subsets in bronchoalveolar lavage fluid from interstitial lung diseases

Pathological Roles of Pulmonary Cells in Acute Lung Injury: Lessons from Clinical Practice

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