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Single-cell analyses highlight the proinflammatory contribution of C1q-high monocytes to Behçet’s disease

Behçet’s disease (BD) is a chronic vasculitis characterized by systemic immune aberrations. However, a comprehensive understanding of immune disturbances in BD and how they contribute to BD pathogenesis is lacking. Here, we performed single-cell and bulk RNA sequencing to profile peripheral blood mo...

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Autores principales: Zheng, Wenjie, Wang, Xiaoman, Liu, Jinjing, Yu, Xin, Li, Lu, Wang, Heping, Yu, Jijun, Pei, Xiaoya, Li, Chaoran, Wang, Zhimian, Zhang, Menghao, Zeng, Xiaofeng, Zhang, Fengchun, Wang, Chenfei, Chen, Hua, Chen, Hou-Zao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245671/
https://www.ncbi.nlm.nih.gov/pubmed/35727985
http://dx.doi.org/10.1073/pnas.2204289119
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author Zheng, Wenjie
Wang, Xiaoman
Liu, Jinjing
Yu, Xin
Li, Lu
Wang, Heping
Yu, Jijun
Pei, Xiaoya
Li, Chaoran
Wang, Zhimian
Zhang, Menghao
Zeng, Xiaofeng
Zhang, Fengchun
Wang, Chenfei
Chen, Hua
Chen, Hou-Zao
author_facet Zheng, Wenjie
Wang, Xiaoman
Liu, Jinjing
Yu, Xin
Li, Lu
Wang, Heping
Yu, Jijun
Pei, Xiaoya
Li, Chaoran
Wang, Zhimian
Zhang, Menghao
Zeng, Xiaofeng
Zhang, Fengchun
Wang, Chenfei
Chen, Hua
Chen, Hou-Zao
author_sort Zheng, Wenjie
collection PubMed
description Behçet’s disease (BD) is a chronic vasculitis characterized by systemic immune aberrations. However, a comprehensive understanding of immune disturbances in BD and how they contribute to BD pathogenesis is lacking. Here, we performed single-cell and bulk RNA sequencing to profile peripheral blood mononuclear cells (PBMCs) and isolated monocytes from BD patients and healthy donors. We observed prominent expansion and transcriptional changes in monocytes in PBMCs from BD patients. Deciphering the monocyte heterogeneity revealed the accumulation of C1q-high (C1q(hi)) monocytes in BD. Pseudotime inference indicated that BD monocytes markedly shifted their differentiation toward inflammation-accompanied and C1q(hi) monocyte–ended trajectory. Further experiments showed that C1q(hi) monocytes enhanced phagocytosis and proinflammatory cytokine secretion, and multiplatform analyses revealed the significant clinical relevance of this subtype. Mechanistically, C1q(hi) monocytes were induced by activated interferon-γ (IFN-γ) signaling in BD patients and were decreased by tofacitinib treatment. Our study illustrates the BD immune landscape and the unrecognized contribution of C1q(hi) monocytes to BD hyperinflammation, showing their potential as therapeutic targets and clinical assessment indexes.
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spelling pubmed-92456712022-12-21 Single-cell analyses highlight the proinflammatory contribution of C1q-high monocytes to Behçet’s disease Zheng, Wenjie Wang, Xiaoman Liu, Jinjing Yu, Xin Li, Lu Wang, Heping Yu, Jijun Pei, Xiaoya Li, Chaoran Wang, Zhimian Zhang, Menghao Zeng, Xiaofeng Zhang, Fengchun Wang, Chenfei Chen, Hua Chen, Hou-Zao Proc Natl Acad Sci U S A Biological Sciences Behçet’s disease (BD) is a chronic vasculitis characterized by systemic immune aberrations. However, a comprehensive understanding of immune disturbances in BD and how they contribute to BD pathogenesis is lacking. Here, we performed single-cell and bulk RNA sequencing to profile peripheral blood mononuclear cells (PBMCs) and isolated monocytes from BD patients and healthy donors. We observed prominent expansion and transcriptional changes in monocytes in PBMCs from BD patients. Deciphering the monocyte heterogeneity revealed the accumulation of C1q-high (C1q(hi)) monocytes in BD. Pseudotime inference indicated that BD monocytes markedly shifted their differentiation toward inflammation-accompanied and C1q(hi) monocyte–ended trajectory. Further experiments showed that C1q(hi) monocytes enhanced phagocytosis and proinflammatory cytokine secretion, and multiplatform analyses revealed the significant clinical relevance of this subtype. Mechanistically, C1q(hi) monocytes were induced by activated interferon-γ (IFN-γ) signaling in BD patients and were decreased by tofacitinib treatment. Our study illustrates the BD immune landscape and the unrecognized contribution of C1q(hi) monocytes to BD hyperinflammation, showing their potential as therapeutic targets and clinical assessment indexes. National Academy of Sciences 2022-06-21 2022-06-28 /pmc/articles/PMC9245671/ /pubmed/35727985 http://dx.doi.org/10.1073/pnas.2204289119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Zheng, Wenjie
Wang, Xiaoman
Liu, Jinjing
Yu, Xin
Li, Lu
Wang, Heping
Yu, Jijun
Pei, Xiaoya
Li, Chaoran
Wang, Zhimian
Zhang, Menghao
Zeng, Xiaofeng
Zhang, Fengchun
Wang, Chenfei
Chen, Hua
Chen, Hou-Zao
Single-cell analyses highlight the proinflammatory contribution of C1q-high monocytes to Behçet’s disease
title Single-cell analyses highlight the proinflammatory contribution of C1q-high monocytes to Behçet’s disease
title_full Single-cell analyses highlight the proinflammatory contribution of C1q-high monocytes to Behçet’s disease
title_fullStr Single-cell analyses highlight the proinflammatory contribution of C1q-high monocytes to Behçet’s disease
title_full_unstemmed Single-cell analyses highlight the proinflammatory contribution of C1q-high monocytes to Behçet’s disease
title_short Single-cell analyses highlight the proinflammatory contribution of C1q-high monocytes to Behçet’s disease
title_sort single-cell analyses highlight the proinflammatory contribution of c1q-high monocytes to behçet’s disease
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245671/
https://www.ncbi.nlm.nih.gov/pubmed/35727985
http://dx.doi.org/10.1073/pnas.2204289119
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