The paper present a comprehensive single-cell immune atlas comparing immune architecture and activity in second-trimester fetuses and adults across multiple organs. This research challenges the idea of fetal immune quiescence by uncovering widespread memory and activated T cells, alongside evidence of T-cell receptor (TCR) clonal sharing across various organs, including barrier sites. The study identifies specific immune tolerance mechanisms in the fetus, notably involving ARG1+ neutrophils and the PTGES3-PTGER4 signaling pathway, which actively suppress T cell activation. Furthermore, it details the widespread distribution of functional hematopoietic stem cells (HSCs) in both traditional and non-canonical organs, underscoring a dynamic, systemic immune maturation process during fetal development.

References:

• He S, Luo C L, Luo T, et al. Systemic immune activity occurs during human immune system maturation[J]. Cell, 2025.