Single-cell transcriptomics unveil profiles and interplay of immune subsets in rare autoimmune childhood Sjogren's disease.

Childhood Sjogren's disease represents critically unmet medical needs due to a complete lack of immunological and molecular characterizations. This study presents key immune cell subsets and their interactions in the periphery in childhood Sjogren's disease. Here we show that single-cell RNA sequencing identifies the subsets of IFN gene-enriched monocytes, CD4(+) T effector memory, and XCL1(+) NK cells as potential key players in childhood Sjogren's disease, and especially in those with recurrent parotitis, which is the chief symptom prompting clinical visits from young children. A unique cluster of monocytes with type I and II IFN-related genes is identified in childhood Sjogren's disease, compared to the age-matched control. In vitro regulatory T cell functional assay demonstrates intact functionality in childhood Sjogren's disease in contrast to reduced suppression in adult Sjogren's disease. Mapping this transcriptomic landscape and interplay of immune cell subsets will expedite the understanding of childhood Sjogren's disease pathogenesis and set the foundation for precision medicine.