Alternative activation in systemic juvenile idiopathic arthritis monocytes

Claudia Macaubas, Khoa D. Nguyen, Ariana Peck, Julia Buckingham, Chetan Deshpande, Elizabeth Wong, Heather C. Alexander, Sheng Yung Chang, Ann Begovich, Yue Sun, Jane L. Park, Kuang Hung Pan, Richard Lin, Chih Jian Lih, Erin M. Augustine, Carolyn Phillips, Andreas V. Hadjinicolaou, Tzielan Lee, Elizabeth D. Mellins*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Systemic juvenile idiopathic arthritis (SJIA) is a chronic autoinflammatory condition. The association with macrophage activation syndrome, and the therapeutic efficacy of inhibiting monocyte-derived cytokines, has implicated these cells in SJIA pathogenesis. To characterize the activation state (classical/M1 vs. alternative/M2) of SJIA monocytes, we immunophenotyped monocytes using several approaches. Monocyte transcripts were analyzed by microarray and quantitative PCR. Surface proteins were measured at the single cell level using flow cytometry. Cytokine production was evaluated by intracellular staining and ELISA. CD14 ++CD16 - and CD14 +CD16 + monocyte subsets are activated in SJIA. A mixed M1/M2 activation phenotype is apparent at the single cell level, especially during flare. Consistent with an M2 phenotype, SJIA monocytes produce IL-1β after LPS exposure, but do not secrete it. Despite the inflammatory nature of active SJIA, circulating monocytes demonstrate significant anti-inflammatory features. The persistence of some of these phenotypes during clinically inactive disease argues that this state reflects compensated inflammation.

Original languageEnglish (US)
Pages (from-to)362-372
Number of pages11
JournalClinical Immunology
Volume142
Issue number3
DOIs
StatePublished - Mar 2012

Keywords

  • Activation phenotype
  • Cytokines
  • Juvenile arthritis
  • Monocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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