Single-Cell Atlas of Fetal Immunity Across Lung, Spleen, and Umbilical Cord Blood in Nonhuman Primates
Description
The fetal immune system develops within a tightly regulated environment that balances immune tolerance with readiness for postnatal antigen exposure. However, limited fetal tissue access constrains understanding of immune ontogeny across compartments. Here we present a multi-tissue single-cell transcriptional atlas of the late-gestation (GD130-135) rhesus macaque fetal immune system, profiling leukocytes from lung, spleen, and umbilical cord blood (UCBMC) spanning myeloid, lymphoid, innate lymphoid, and hematopoietic stem cell lineages. Fetal lung is enriched in myeloid cells and ILC2s and shows a proinflammatory communication bias. Spleen is dominated by T and B cells, with B cells showing signatures of V(D)J recombination and isotype switching and CD4 T cells showing increased activation and Treg frequency. UCBMC is predominantly composed of T cells with a regulatory immune landscape. Spectral flow cytometry and functional assays corroborate these tissue-specific differences revealing elevated basal secretion of inflammatory mediators in fetal lung, while spleen and UCBMC show greater inducible responses following stimulation. Together, this study provides a comprehensive cross-tissue atlas of late-gestation primate fetal immunity, revealing coordinated tissue-specific immune specialization, functional capacity, and intercellular communication networks that shape immune readiness prior to birth.