Single-cell transcriptomics highlights the proinflammatory contribution of C1q-high monocytes to Behçet’s disease

Behçet’s disease (BD) is a chronic vasculitis characterized by systemic immune aberrations. Here, we performed single-cell 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 multi-platform analyses revealed the significant clinical relevance of this subtype. Mechanistically, C1qhi monocytes were induced by activated IFN-γ signaling in BD patients, and were decreased by tofacitinib treatment. Our study illustrates BD immune landscape and the unrecognized contribution of C1qhi monocytes to BD hyperinflammation, showing their potential as therapeutic targets and clinical assessment indexes. This dataset contains single-cell sequencing results of PBMCs (BD: n=4, HC: n=4) and isolated CD14+monocytes (BD: n=4, HC: n=4) . Please note that raw data are not provided as they are derived from human subjects. ***Raw data not available due to patient privacy concerns***