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 language | English (US) |
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Pages (from-to) | 362-372 |
Number of pages | 11 |
Journal | Clinical Immunology |
Volume | 142 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2012 |
Funding
This study was supported by The Wasie Foundation , the Dana Foundation , the Child Health Research Program of Stanford University , the National Institutes of Health (to EM), the American College of Rheumatology Research and Education Physician Scientist Development Award , the Ernest and Amelia Gallo Endowed Postdoctoral Fellowship Fund , and NIAMS T32AR050942 (to JLP).
Keywords
- Activation phenotype
- Cytokines
- Juvenile arthritis
- Monocytes
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology