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...

Full description

Saved in:
Bibliographic Details
Published inProceedings of the National Academy of Sciences - PNAS Vol. 119; no. 26; pp. 1 - 12
Main Authors 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
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 28.06.2022
Subjects
Behcet Syndrome - genetics
Behcet Syndrome - immunology
Behcet's syndrome
Biological Sciences
Complement C1q - genetics
Complement C1q - immunology
Cytokines
Gene sequencing
Heterogeneity
Humans
Inflammation
Interferon
Leukocytes (mononuclear)
Monocytes
Monocytes - immunology
Pathogenesis
Patients
Peripheral blood mononuclear cells
Phagocytosis
RNA-Seq
Single-Cell Analysis
Therapeutic targets
Vasculitis
Vein & artery diseases
γ-Interferon
monocytes
Behçet’s disease
interferon
single-cell analysis
Online AccessGet full text

Cover

More Information
Summary: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 (C1qhi) monocytes in BD. Pseudotime inference indicated that BD monocytes markedly shifted their differentiation toward inflammation-accompanied and C1qhi monocyte–ended trajectory. Further experiments showed that C1qhi monocytes enhanced phagocytosis and proinflammatory cytokine secretion, and multiplatform analyses revealed the significant clinical relevance of this subtype. Mechanistically, C1qhi 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 C1qhi monocytes to BD hyperinflammation, showing their potential as therapeutic targets and clinical assessment indexes.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
Author Contributions: W.Z., X.W., and H.-Z.C. conceptualized and designed the project; X.W. conducted the bioinformatics analysis with help from H.W., J.Y., and X.P.; J.L. and X.Y. performed scRNA-seq and immunological experiments; L.L., C.L., Z.W., and M.Z. participated in the sample collection; X.W. and X.Y. drafted the manuscript with help from W.Z., H.C., and H.-Z.C.; X.Z., F.Z., and C.W. reviewed the manuscript and provided valuable suggestions.
1W.Z., X.W., J.L., and X.Y. contributed equally to this work.
Edited by Yuta Kochi, Rikagaku Kenkyujo; received March 24, 2022; accepted April 15, 2022 by Editorial Board Member Tadatsugu Taniguchi
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.2204289119