TLR engagement induces ARID3a in human blood hematopoietic progenitors and modulates IFNα production

Cell Immunol. 2020 Nov:357:104201. doi: 10.1016/j.cellimm.2020.104201. Epub 2020 Sep 9.

Abstract

The DNA binding protein AT-rich interacting domain 3a (ARID3a)2 is expressed in healthy human hematopoietic cord blood progenitors where its modulation influences myeloid versus B lineage development. ARID3a is also variably expressed in subsets of adult peripheral blood hematopoietic progenitors where the consequences of ARID3a expression are unknown. In B lymphocytes, Toll-like receptor (TLR)3 signaling induces ARID3a expression in association with Type I interferon inflammatory cytokines. We hypothesized that TLR ligand stimulation of peripheral blood hematopoietic progenitors would induce ARID3a expression resulting in interferon production, and potentially influencing lineage decisions. Our data revealed that the TLR9 agonist CpG induces ARID3a expression with interferon alpha synthesis in human hematopoietic progenitors. However, ARID3a expression was not associated with increased B lineage development. These results demonstrate the need for further experiments to better define how pathogen-associated responses influence hematopoiesis.

Keywords: ARID3a; Hematopoiesis; Innate immunity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism
  • CpG Islands
  • Cytokines / metabolism
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / blood
  • Female
  • Flow Cytometry / methods
  • Gene Expression
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Interferon-alpha / biosynthesis*
  • Interferon-alpha / genetics
  • Interferon-alpha / immunology
  • Ligands
  • Middle Aged
  • Signal Transduction
  • Toll-Like Receptors / blood*
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / biosynthesis*
  • Transcription Factors / blood

Substances

  • ARID3A protein, human
  • Cytokines
  • DNA-Binding Proteins
  • Interferon-alpha
  • Ligands
  • Toll-Like Receptors
  • Transcription Factors