A multidimensional blood stimulation assay reveals immune alterations underlying systemic juvenile idiopathic arthritis. Academic Article uri icon

Overview

abstract

  • The etiology of sporadic human chronic inflammatory diseases remains mostly unknown. To fill this gap, we developed a strategy that simultaneously integrates blood leukocyte responses to innate stimuli at the transcriptional, cellular, and secreted protein levels. When applied to systemic juvenile idiopathic arthritis (sJIA), an autoinflammatory disease of unknown etiology, this approach identified gene sets associated with specific cytokine environments and activated leukocyte subsets. During disease remission and off treatment, sJIA patients displayed dysregulated responses to TLR4, TLR8, and TLR7 stimulation. Isolated sJIA monocytes underexpressed the IL-1 inhibitor aryl hydrocarbon receptor (AHR) at baseline and accumulated higher levels of intracellular IL-1β after stimulation. Supporting the demonstration that AHR down-regulation skews monocytes toward macrophage differentiation, sJIA monocytes differentiated in vitro toward macrophages, away from the dendritic cell phenotype. This might contribute to the increased incidence of macrophage activation syndrome in these patients. Integrated analysis of high-dimensional data can thus unravel immune alterations predisposing to complex inflammatory diseases.

publication date

  • September 21, 2017

Research

keywords

  • Arthritis, Juvenile
  • Cell Differentiation
  • Macrophages
  • Monocytes

Identity

PubMed Central ID

  • PMC5679164

Scopus Document Identifier

  • 85033399059

Digital Object Identifier (DOI)

  • 10.1038/nrclinonc.2014.6

PubMed ID

  • 28935693

Additional Document Info

volume

  • 214

issue

  • 11