Myeloid differentiation architecture of leukocyte transcriptome dynamics in perceived social isolation.
Title | Myeloid differentiation architecture of leukocyte transcriptome dynamics in perceived social isolation. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Cole SW, Capitanio JP, Chun K, Arevalo JMG, Ma J, Cacioppo JT |
Journal | Proc Natl Acad Sci U S A |
Volume | 112 |
Issue | 49 |
Pagination | 15142-7 |
Date Published | 2015 Dec 8 |
ISSN | 1091-6490 |
Keywords | Animals, Cell Differentiation, Leukocytes, Macaca mulatta, Myeloid Cells, Social Isolation, Transcriptome |
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. |
DOI | 10.1073/pnas.1514249112 |
Alternate Journal | Proc. Natl. Acad. Sci. U.S.A. |
PubMed ID | 26598672 |
PubMed Central ID | PMC4679065 |
Grant List | P01-AG18911 / AG / NIA NIH HHS / United States P30 AG028748 / AG / NIA NIH HHS / United States P30-AG017265 / AG / NIA NIH HHS / United States P30-AG028748 / AG / NIA NIH HHS / United States P51-OD011107 / OD / NIH HHS / United States R01-AG034052 / AG / NIA NIH HHS / United States R01-DA024441 / DA / NIDA NIH HHS / United States R37-AG033590 / AG / NIA NIH HHS / United States |