Alternative activation in systemic juvenile idiopathic arthritis monocytes

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

来源：Clinical Immunology, 2012, 142(3): 362-372.

DOI：10.1016/j.clim.2011.12.008

• Juvenile arthritis
• Monocytes
• Activation phenotype
• Cytokines

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 lL-1 beta 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.

• 出版日期2012-3