AUTHOR=Peterson Laura S. , Hedou Julien , Ganio Edward A. , Stelzer Ina A. , Feyaerts Dorien , Harbert Eliza , Adusumelli Yamini , Ando Kazuo , Tsai Eileen S. , Tsai Amy S. , Han Xiaoyuan , Ringle Megan , Houghteling Pearl , Reiss Jonathan D. , Lewis David B. , Winn Virginia D. , Angst Martin S. , Aghaeepour Nima , Stevenson David K. , Gaudilliere Brice TITLE=Single-Cell Analysis of the Neonatal Immune System Across the Gestational Age Continuum JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.714090 DOI=10.3389/fimmu.2021.714090 ISSN=1664-3224 ABSTRACT=

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.