To investigate how dendritic cells (DCs) are remodeled in health and disease, we generated a blood single-cell DC atlas from ~400 donors across the human lifespan (2 months to 105 years) and in the contexts of vaccination, SARS-CoV-2 and RSV infection, and childhood-onset systemic lupus erythematosus (cSLE).
Across the lifespan, infants had fewer conventional DCs (cDCs) and a higher proportion of plasmacytoid DCs (pDCs), which made up ~53% of total DCs. In contrast, older adults were enriched for cDC2 (~49% of DCs) and monocyte-derived DCs (moDCs; ~11%). After initial immunization vaccines, cDCs from 2-month-old infants showed an ISGhigh signature at day 7, contrasting with a day 1 signature observed in young and older adults upon flu vaccination. The infant signature resolved one-month post-vaccination. SARS-CoV-2 and RSV-infected infants had reduced cDC frequencies, and infants suffering from severe infectious diseases had more ISGhigh pDCs than convalescent or healthy infants.
In cSLE, we identified 13 DC clusters, including AXL+ DCs. Within this patient cohort, pDC-like cells were enriched, whereas cDCs were more prevalent in healthy children. cSLE DCs also contained a larger proportion of IL1B+ISG+ cells, a phenotype previously observed in cSLE CD14+ monocytes. Longitudinal scRNA-seq of PBMCs from patients with cSLE and matched controls confirmed both the pDC-like bias of AXL+ DCs and the expansion of IL1B+ISG+ DCs in cSLE.
This atlas provides a resource for identifying blood DC subsets that shape immune responses across the lifespan and in disease.