Single-cell Landscape of T Cell Heterogeneity in Kawasaki Disease: STAT3/JAK Axis Regulates the Lineage Differentiation Bias of Th17 Cells

Abstract

BackgroundKawasaki disease (KD) is a pediatric systemic vasculitis in which T-cell-mediated immune responses play a pivotal role. However, the precise dynamic evolution of T-cell subsets during disease progression remains poorly understood. MethodsSingle-cell RNA sequencing (scRNA-seq) was employed to perform high-resolution annotation of peripheral blood mononuclear cells (PBMCs) from healthy controls and KD patients, both pre- and post- IVIG treatment. T-cell developmental trajectories were reconstructed via Monocle3-based pseudotime analysis. Furthermore, the functional significance of the significant pathway was validated in a CAWS-induced KD murine model. ResultsA high-resolution single-cell landscape identified 13 distinct T-cell subtypes. Pseudotime analysis revealed a significant lineage commitment of CD4+ T cells toward a Th17 phenotype during the acute phase of KD, synchronized with the transcriptional upregulation of the STAT3/JAK signaling axis. Animal experiments further demonstrated that pharmacological inhibition of this pathway substantially attenuated inflammatory infiltration in the cardiac vasculature of KD mice. ConclusionThis study identifies the STAT3/JAK-mediated Th17 differentiation bias as a potential regulatory program associated with acute inflammation in Kawasaki disease, thereby highlighting the STAT3/JAK axis as a potential therapeutic target.