A multidimensional blood stimulation assay reveals immune alterations underlying systemic juvenile idiopathic arthritis.
Document Type
Article
Publication Date
11-6-2017
JAX Source
J Exp Med 2017 Nov 6; 214(11):3449-3466.
Volume
214
Issue
11
First Page
3449
Last Page
3466
ISSN
1540-9538
PMID
28935693
DOI
https://doi.org/10.1084/jem.20170412
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. J Exp Med 2017 Nov 6; 214(11):3449-3466.
Recommended Citation
Cepika A,
Banchereau R,
Segura E,
Ohouo M,
Cantarel B,
Goller K,
Cantrell V,
Ruchaud E,
Gatewood E,
Nguyen P,
Gu J,
Anguiano E,
Zurawski S,
Baisch J,
Punaro M,
Baldwin N,
Obermoser G,
Palucka K,
Banchereau J,
Amigorena S,
Pascual V.
A multidimensional blood stimulation assay reveals immune alterations underlying systemic juvenile idiopathic arthritis. J Exp Med 2017 Nov 6; 214(11):3449-3466.