Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS&PUMC), 100730 Beijing, China.
National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science and Technology, 100730 Beijing, China.
Proc Natl Acad Sci U S A. 2022 Jun 28;119(26):e2204289119. doi: 10.1073/pnas.2204289119. Epub 2022 Jun 21.
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) monocytes in BD. Pseudotime inference indicated that BD monocytes markedly shifted their differentiation toward inflammation-accompanied and C1q monocyte-ended trajectory. Further experiments showed that C1q monocytes enhanced phagocytosis and proinflammatory cytokine secretion, and multiplatform analyses revealed the significant clinical relevance of this subtype. Mechanistically, C1q 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 monocytes to BD hyperinflammation, showing their potential as therapeutic targets and clinical assessment indexes.
贝赫切特病（BD）是一种以全身免疫异常为特征的慢性血管炎。然而，人们对 BD 中的免疫紊乱及其如何导致 BD 发病机制仍缺乏全面了解。在这里，我们进行了单细胞和批量 RNA 测序，以描绘 BD 患者和健康供体的外周血单核细胞（PBMC）和分离的单核细胞。我们观察到 BD 患者 PBMC 中的单核细胞明显扩增和转录变化。解析单核细胞异质性揭示了 BD 中 C1q-高（C1q）单核细胞的积累。拟时推断表明，BD 单核细胞明显向炎症伴随和 C1q 单核细胞结束的分化轨迹转移。进一步的实验表明，C1q 单核细胞增强了吞噬作用和促炎细胞因子的分泌，多平台分析显示了这种亚型的显著临床相关性。在机制上，BD 患者中 C1q 单核细胞由活化的干扰素-γ（IFN-γ）信号诱导，并用托法替尼治疗减少。我们的研究说明了 BD 的免疫景观以及 C1q 单核细胞对 BD 过度炎症的未被认识的贡献，表明它们有作为治疗靶点和临床评估指标的潜力。
