title: 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.affiliation: Department of Pediatrics, Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Macaubas
authors.forename: Khoa D
authors.initials: KD
authors.lastname: Nguyen
authors.forename: Ariana
authors.initials: A
authors.lastname: Peck
authors.forename: Julia
authors.initials: J
authors.lastname: Buckingham
authors.forename: Chetan
authors.initials: C
authors.lastname: Deshpande
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Wong
authors.forename: Heather C
authors.initials: HC
authors.lastname: Alexander
authors.forename: Sheng-Yung
authors.initials: SY
authors.lastname: Chang
authors.forename: Ann
authors.initials: A
authors.lastname: Begovich
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.forename: Jane L
authors.initials: JL
authors.lastname: Park
authors.forename: Kuang-Hung
authors.initials: KH
authors.lastname: Pan
authors.forename: Richard
authors.initials: R
authors.lastname: Lin
authors.forename: Chih-Jian
authors.initials: CJ
authors.lastname: Lih
authors.forename: Erin M
authors.initials: EM
authors.lastname: Augustine
authors.forename: Carolyn
authors.initials: C
authors.lastname: Phillips
authors.forename: Andreas V
authors.initials: AV
authors.lastname: Hadjinicolaou
authors.forename: Tzielan
authors.initials: T
authors.lastname: Lee
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Mellins
mesh_terms: D001171:Arthritis, Juvenile / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D058851:GPI-Linked Proteins / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D010641:Phenotype; D017452:Receptors, IgG / Q000276:immunology
chemical_list: D016207:Cytokines; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG