biostudies-literaturePeterson LSDoris Duke Charitable FoundationNIGMS NIH HHS714090https://www.ebi.ac.uk/biostudies/studies/S-EPMC8420969biostudies-literatureUnknown12Although most causes of death and morbidity in premature infants are related to immune maladaptation, the premature immune system remains poorly understood. We provide a comprehensive single-cell depiction of the neonatal immune system at birth across the spectrum of viable gestational age (GA), ranging from 25 weeks to term. A mass cytometry immunoassay interrogated all major immune cell subsets, including signaling activity and responsiveness to stimulation. An elastic net model described the relationship between GA and immunome (R=0.85, p=8.75e-14), and unsupervised clustering highlighted previously unrecognized GA-dependent immune dynamics, including decreasing basal MAP-kinase/NFκB signaling in antigen presenting cells; increasing responsiveness of cytotoxic lymphocytes to interferon-α; and decreasing frequency of regulatory and invariant T cells, including NKT-like cells and CD8⁺CD161⁺ T cells. Knowledge gained from the analysis of the neonatal immune landscape across GA provides a mechanistic framework to understand the unique susceptibility of preterm infants to both hyper-inflammatory diseases and infections.Frontiers in immunologySingle-Cell Analysis of the Neonatal Immune System Across the Gestational Age Continuum.PMC84209692018100R35 GM137936R35 GM138353Feyaerts DHoughteling PTsai ASStelzer IATsai ESHan XAghaeepour NAndo KLewis DBAngst MSGaudilliere BReiss JDHarbert ERingle MWinn VDHedou JAdusumelli YPeterson LSGanio EAStevenson DKfalseSingle-Cell Analysis of the Neonatal Immune System Across the Gestational Age Continuum.Although most causes of death and morbidity in premature infants are related to immune maladaptation, the premature immune system remains poorly understood. We provide a comprehensive single-cell depiction of the neonatal immune system at birth across the spectrum of viable gestational age (GA), ranging from 25 weeks to term. A mass cytometry immunoassay interrogated all major immune cell subsets, including signaling activity and responsiveness to stimulation. An elastic net model described the relationship between GA and immunome (R=0.85, p=8.75e-14), and unsupervised clustering highlighted previously unrecognized GA-dependent immune dynamics, including decreasing basal MAP-kinase/NFκB signaling in antigen presenting cells; increasing responsiveness of cytotoxic lymphocytes to interferon-α; and decreasing frequency of regulatory and invariant T cells, including NKT-like cells and CD8⁺CD161⁺ T cells. Knowledge gained from the analysis of the neonatal immune landscape across GA provides a mechanistic framework to understand the unique susceptibility of preterm infants to both hyper-inflammatory diseases and infections.2021-01-01T00:00:00Z20212026-03-12T23:30:04.178Z2025-08-12T03:04:48.97ZS-EPMC84209693449761010.3389/fimmu.2021.714090