A multidimensional blood stimulation assay reveals immune alterations underlying systemic juvenile idiopathic arthritis

Alma Martina Cepika, Romain Banchereau, Elodie Segura, Marina Ohouo, Brandi Cantarel, Kristina Goller, Victoria Cantrell, Emily Ruchaud, Elizabeth Gatewood, Phuong Nguyen, Jinghua Gu, Esperanza Anguiano, Sandra Zurawski, Jeanine M. Baisch, Marilynn Punaro, Nicole Baldwin, Gerlinde Obermoser, Karolina Palucka, Jacques Banchereau, Sebastian AmigorenaVirginia Pascual

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3449-3466
Number of pages18
JournalJournal of Experimental Medicine
Volume214
Issue number11
DOIs
StatePublished - Nov 1 2017

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Cepika, A. M., 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. M., Punaro, M., Baldwin, N., Obermoser, G., Palucka, K., Banchereau, J., ... Pascual, V. (2017). A multidimensional blood stimulation assay reveals immune alterations underlying systemic juvenile idiopathic arthritis. Journal of Experimental Medicine, 214(11), 3449-3466. https://doi.org/10.1084/jem.20170412