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Nussbaum, C.

Publications and source records attributed to Nussbaum, C..

2 recordsLinked to original sources

Development of circadian immune regulation in early life

Circadian rhythms temporally regulate immune cell trafficking, abundance, and immune responsiveness in adults, yet how this rhythmic organization emerges during postnatal development remains unknown. Here, we systematically investigated the establishment and development of circadian immune regulation across multiple biological levels. Leukocyte rhythmicity was not present at birth but was gradually established and strengthened during postnatal development in a leukocyte subset-dependent manner. In parallel, promigratory markers displayed dynamic and heterogeneous developmental trajectories, indicating progressive coordination of rhythmic promigratory programs. At the systemic level, peripheral clocks matured and synchronized during development, with tissue- and clock-gene-dependent differences in the acquisition timing, peak phase, and amplitude of circadian oscillations. This multi-level analysis identifies postnatal development as a dynamic period during which circadian immunity is progressively consolidated through leukocyte rhythmicity, regulation of promigratory factors, and peripheral clocks.

immunology↗

Human neonatal CITE-seq atlas identifies an immune transition at 32 weeks' gestation from CD15+ myeloid-dominated to interferon-primed immunity

The human neonatal immune system is developmentally specialized to balance the unique requirements of perinatal transition. Disruption of this finely tuned balance, as in preterm birth, may have profound consequences for immunity and overall health. However, the impact of prematurity on immune composition and functional responsiveness across gestational ages (GA) remains incompletely understood. Single-cell profiling has advanced our understanding of neonatal immunity, yet most studies were limited to unimodal readouts, narrow GA windows, or baseline function. Here, we present a comprehensive human neonatal CITE-seq atlas (82 samples from 25 neonates and 10 adults as controls) at the first days of life covering a wide GA range and integrating baseline and stimulated conditions. Most notably, we identify a GA-dependent immune transition point centered around 32 weeks of GA, which discriminates extremely and very preterm neonates (GA <32wks) from those of higher GA ([&ge;]32wks). In particular, early-life immunity in extremely and very preterm infants showed CD15+ granulocytic myeloid derived suppressor cell-like predominance, whereas more mature neonates exhibited interferon-primed transcriptional profiles. This resulted in divergent myeloid-to-lymphocyte signaling networks and qualitatively distinct NK- and T-cell bystander responses upon activation. Together, these findings show that intrauterine development imprints GA-specific immune programs. By defining a developmental transition around a GA of 32 weeks that regulates baseline and induced responses of neonatal immune cells, our atlas provides a framework for understanding the vulnerability of preterm infants and thus may pave the way for developing GA-adapted immunomodulatory strategies. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/715643v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@1d2ce73org.highwire.dtl.DTLVardef@f02194org.highwire.dtl.DTLVardef@12cb15eorg.highwire.dtl.DTLVardef@130ca51_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗