Single-cell transcriptomics reveals metabolic reprogramming of peripheral blood monocytes in pediatric ANCA-associated vasculitis

Metabolic reprogramming is central to regulating immune cell function in immune-related diseases. To assess the metabolic modifications in immune cells in ANCA-associated vasculitis (AAV), we obtained peripheral blood samples from pediatric AAV patients for single-cell RNA sequencing. Single-cell flux estimation analysis revealed that the fatty acid-to-acetyl-CoA metabolic flux was remarkably elevated in monocytes of the AAV group, and the level of the related metabolite, acetyl-CoA, was also increased. Pseudotime analysis revealed that acyl-CoA synthetase long-chain family member 4 ( ACSL4 ) was increased markedly in monocytes in AAV. Quantitative reverse transcription polymerase chain reaction displayed that the mRNA level of ACSL4 in monocytes was noticeably elevated compared to that in the control group. SCENIC analysis identified CUT-like homeobox 1 (CUX1) as one of the most active transcription factors in monocytes, with ACSL4 being its target gene. Cell–cell communication analysis illustrated that the TGF-β and CD48 signaling pathways were remarkably augmented in monocytes of AAV patients compared to the control group. Moreover, both TGF-β and CD48 signals from monocytes were transmitted to classical dendritic cells. Our findings reveal that fatty acid metabolism is markedly reprogrammed in peripheral blood monocytes in AAV, highlighting a potential metabolic mechanism underlying disease pathogenesis. As such, this study provides a metabolic perspective on the potential pathogenic mechanisms through which monocytes contribute to the onset of AAV and organ damage, offering new insights into therapeutic strategies for AAV.