title: Myeloid differentiation architecture of leukocyte transcriptome dynamics in perceived social isolation.
abstract: To define the cellular mechanisms of up-regulated inflammatory gene expression and down-regulated antiviral response in people experiencing perceived social isolation (loneliness), we conducted integrative analyses of leukocyte gene regulation in humans and rhesus macaques. Five longitudinal leukocyte transcriptome surveys in 141 older adults showed up-regulation of the sympathetic nervous system (SNS), monocyte population expansion, and up-regulation of the leukocyte conserved transcriptional response to adversity (CTRA). Mechanistic analyses in a macaque model of perceived social isolation confirmed CTRA activation and identified selective up-regulation of the CD14(++)/CD16(-) classical monocyte transcriptome, functional glucocorticoid desensitization, down-regulation of Type I and II interferons, and impaired response to infection by simian immunodeficiency virus (SIV). These analyses identify neuroendocrine-related alterations in myeloid cell population dynamics as a key mediator of CTRA transcriptome skewing, which may both propagate perceived social isolation and contribute to its associated health risks.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095; Norman Cousins Center, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095;
authors.forename: Steven W
authors.initials: SW
authors.lastname: Cole
authors.affiliation: Department of Psychology, University of California, Davis, CA 95616; California National Primate Research Center, University of California, Davis, CA 95616;
authors.forename: John P
authors.initials: JP
authors.lastname: Capitanio
authors.affiliation: Department of Psychology, University of California, Davis, CA 95616; California National Primate Research Center, University of California, Davis, CA 95616;
authors.forename: Katie
authors.initials: K
authors.lastname: Chun
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095; Norman Cousins Center, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095;
authors.forename: Jesusa M G
authors.initials: JM
authors.lastname: Arevalo
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095; Norman Cousins Center, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095;
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Ma
authors.affiliation: Center for Cognitive and Social Neuroscience, University of Chicago, Chicago, IL 60637; Department of Psychology, University of Chicago, Chicago, IL 60637; Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL 60637 Cacioppo@uchicago.edu.
authors.forename: John T
authors.initials: JT
authors.lastname: Cacioppo
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism*; D008253:Macaca mulatta; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism*; D012934:Social Isolation; D059467:Transcriptome
keywords: health; inflammation; loneliness; social genomics