Genomic analysis of progenitors in viral infection implicates glucocorticoids as suppressors of plasmacytoid dendritic cell generation
成果类型：
Article
署名作者：
Jo, Yeara; Greene, Trever T.; Chiale, Carolina; Zhang, Kai; Fang, Ziyan; Dallari, Simone; Marooki, Nuha; Wang, Wei; Zuniga, Elina I.
署名单位：
University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego
刊物名称：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN/ISSBN：
0027-10801
DOI：
10.1073/pnas.2410092122
发表日期：
2025-05-06
关键词：
transcription factors
virus-infection
flt3 ligand
predendritic cells
binding proteins
ifn-alpha/beta
t-lymphocytes
factor e2-2
chromatin
maturation
摘要：
Plasmacytoid Dendritic cells (pDCs) are the most potent producers of interferons, which are critical antiviral cytokines. pDC development is, however, compromised following a viral infection, and this phenomenon, as well as its relationship to conventional (c)DC development is still incompletely understood. By using lymphocytic choriomeningitis virus (LCMV) infection in mice as a model system, we observed that DC progenitors skewed away from pDC and toward cDC development during in vivo viral infection. Subsequent characterization of the transcriptional and epigenetic landscape of fms- like tyrosine kinase 3+ (Flt3+) DC progenitors and follow- up studies revealed increased apoptosis and reduced (IFN- I)- dependent ablation of pre- pDCs, but not pre- DC precursors, after both acute and chronic LCMV infections. In addition, integrated genomic analysis identified altered activity of GCs to DC progenitors led to downregulated pDC- primed- genes while upregulating cDC- primed- genes, and that endogenous GCs selectively decreased pDC, but not cDC, following viral infection and links pDC numbers to the hypothalamic-pituitary-adrenal axis.