Alternative activation in systemic juvenile idiopathic arthritis monocytes.

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.

• Authors: 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
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 142 Issue 3 Pg. 362-72 (Mar 2012) ISSN: 1521-7035 [Electronic] United States
• PMID: 22281427 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Cytokines
• FCGR3B protein, human
• GPI-Linked Proteins
• Lipopolysaccharide Receptors
• Receptors, IgG

Topics

• Arthritis, Juvenile (immunology)
• Cells, Cultured
• Child
• Cytokines (biosynthesis, immunology)
• GPI-Linked Proteins (immunology)
• Gene Expression
• Humans
• Lipopolysaccharide Receptors (immunology)
• Monocytes (immunology)
• Phenotype
• Receptors, IgG (immunology)