A cellular census of human peripheral immune cells identifies novel cell states in lung diseases

Abstract Increasing evidence supports a central role of the immune system in lung diseases. Understanding how immunological alterations between lung diseases provide opportunities for immunotherapy. Exhausted T cells play a key role of immune suppression in lung cancer and chronic obstructive pulmon...

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Autores principales: Dongli Song, Furong Yan, Huirong Fu, Liyang Li, Jie Hao, Zhenhua Zhu, Ling Ye, Yong Zhang, Meiling Jin, Lihua Dai, Hao Fang, Zhenju Song, Duojiao Wu, Xiangdong Wang
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Publicado: Wiley 2021
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Acceso en línea:https://doaj.org/article/30f1393354de4a7a8ab6e6fe1bcf7357
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spelling oai:doaj.org-article:30f1393354de4a7a8ab6e6fe1bcf73572021-11-30T07:25:38ZA cellular census of human peripheral immune cells identifies novel cell states in lung diseases2001-132610.1002/ctm2.579https://doaj.org/article/30f1393354de4a7a8ab6e6fe1bcf73572021-11-01T00:00:00Zhttps://doi.org/10.1002/ctm2.579https://doaj.org/toc/2001-1326Abstract Increasing evidence supports a central role of the immune system in lung diseases. Understanding how immunological alterations between lung diseases provide opportunities for immunotherapy. Exhausted T cells play a key role of immune suppression in lung cancer and chronic obstructive pulmonary disease was proved in our previous study. The present study aims to furthermore define molecular landscapes and heterogeneity of systemic immune cell target proteomic and transcriptomic profiles and interactions between circulating immune cells and lung residential cells in various lung diseases. We firstly measured target proteomic profiles of circulating immune cells from healthy volunteers and patients with stable pneumonia, stable asthma, acute asthma, acute exacerbation of chronic obstructive pulmonary disease, chronic obstructive pulmonary disease and lung cancer, using single‐cell analysis by cytometry by time‐of‐flight with 42 antibodies. The nine immune cells landscape was mapped among those respiratory system diseases, including CD4+ T cells, CD8+ T cells, dendritic cells, B cells, eosinophil, γδT cells, monocytes, neutrophil and natural killer cells. The double‐negative T cells and exhausted CD4+ central memory T cells subset were identified in patients with acute pneumonia. This T subset expressed higher levels of T‐cell immunoglobulin and mucin domain‐containing protein 3 (Tim3) and T‐cell immunoreceptor with Ig and ITIM domains (TIGIT) in patients with acute pneumonia and stable pneumonia. Biological processes and pathways of immune cells including immune response activation, regulation of cell cycle and pathways in cancer in peripheral blood immune cells were defined by bulk RNA sequencing (RNA‐seq). The heterogeneity among immune cells including CD4+, CD8+ T cells and NK T cells by single immune cell RNA‐seq with significant difference was found by single‐cell sequencing. The effect of interstitial telocytes on the immune cell types and immune function was finally studied and the expressions of CD8a and chemokine C–C motif receptor 7 (CCR7) were increased significantly in co‐cultured groups. Our data indicate that proteomic and transcriptomic profiles and heterogeneity of circulating immune cells provides new insights for understanding new molecular mechanisms of immune cell function, interaction and modulation as a source to identify and develop biomarkers and targets for lung diseases.Dongli SongFurong YanHuirong FuLiyang LiJie HaoZhenhua ZhuLing YeYong ZhangMeiling JinLihua DaiHao FangZhenju SongDuojiao WuXiangdong WangWileyarticleacute lung pneumoniaimmunitylung diseasesPD‐1Medicine (General)R5-920ENClinical and Translational Medicine, Vol 11, Iss 11, Pp n/a-n/a (2021)
institution DOAJ
collection DOAJ
language EN
topic acute lung pneumonia
immunity
lung diseases
PD‐1
Medicine (General)
R5-920
spellingShingle acute lung pneumonia
immunity
lung diseases
PD‐1
Medicine (General)
R5-920
Dongli Song
Furong Yan
Huirong Fu
Liyang Li
Jie Hao
Zhenhua Zhu
Ling Ye
Yong Zhang
Meiling Jin
Lihua Dai
Hao Fang
Zhenju Song
Duojiao Wu
Xiangdong Wang
A cellular census of human peripheral immune cells identifies novel cell states in lung diseases
description Abstract Increasing evidence supports a central role of the immune system in lung diseases. Understanding how immunological alterations between lung diseases provide opportunities for immunotherapy. Exhausted T cells play a key role of immune suppression in lung cancer and chronic obstructive pulmonary disease was proved in our previous study. The present study aims to furthermore define molecular landscapes and heterogeneity of systemic immune cell target proteomic and transcriptomic profiles and interactions between circulating immune cells and lung residential cells in various lung diseases. We firstly measured target proteomic profiles of circulating immune cells from healthy volunteers and patients with stable pneumonia, stable asthma, acute asthma, acute exacerbation of chronic obstructive pulmonary disease, chronic obstructive pulmonary disease and lung cancer, using single‐cell analysis by cytometry by time‐of‐flight with 42 antibodies. The nine immune cells landscape was mapped among those respiratory system diseases, including CD4+ T cells, CD8+ T cells, dendritic cells, B cells, eosinophil, γδT cells, monocytes, neutrophil and natural killer cells. The double‐negative T cells and exhausted CD4+ central memory T cells subset were identified in patients with acute pneumonia. This T subset expressed higher levels of T‐cell immunoglobulin and mucin domain‐containing protein 3 (Tim3) and T‐cell immunoreceptor with Ig and ITIM domains (TIGIT) in patients with acute pneumonia and stable pneumonia. Biological processes and pathways of immune cells including immune response activation, regulation of cell cycle and pathways in cancer in peripheral blood immune cells were defined by bulk RNA sequencing (RNA‐seq). The heterogeneity among immune cells including CD4+, CD8+ T cells and NK T cells by single immune cell RNA‐seq with significant difference was found by single‐cell sequencing. The effect of interstitial telocytes on the immune cell types and immune function was finally studied and the expressions of CD8a and chemokine C–C motif receptor 7 (CCR7) were increased significantly in co‐cultured groups. Our data indicate that proteomic and transcriptomic profiles and heterogeneity of circulating immune cells provides new insights for understanding new molecular mechanisms of immune cell function, interaction and modulation as a source to identify and develop biomarkers and targets for lung diseases.
format article
author Dongli Song
Furong Yan
Huirong Fu
Liyang Li
Jie Hao
Zhenhua Zhu
Ling Ye
Yong Zhang
Meiling Jin
Lihua Dai
Hao Fang
Zhenju Song
Duojiao Wu
Xiangdong Wang
author_facet Dongli Song
Furong Yan
Huirong Fu
Liyang Li
Jie Hao
Zhenhua Zhu
Ling Ye
Yong Zhang
Meiling Jin
Lihua Dai
Hao Fang
Zhenju Song
Duojiao Wu
Xiangdong Wang
author_sort Dongli Song
title A cellular census of human peripheral immune cells identifies novel cell states in lung diseases
title_short A cellular census of human peripheral immune cells identifies novel cell states in lung diseases
title_full A cellular census of human peripheral immune cells identifies novel cell states in lung diseases
title_fullStr A cellular census of human peripheral immune cells identifies novel cell states in lung diseases
title_full_unstemmed A cellular census of human peripheral immune cells identifies novel cell states in lung diseases
title_sort cellular census of human peripheral immune cells identifies novel cell states in lung diseases
publisher Wiley
publishDate 2021
url https://doaj.org/article/30f1393354de4a7a8ab6e6fe1bcf7357
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