title: Altered signaling in systemic juvenile idiopathic arthritis monocytes.
abstract: Systemic juvenile idiopathic arthritis (sJIA) is characterized by systemic inflammation and arthritis. Monocytes are implicated in sJIA pathogenesis, but their role in disease is unclear. The response of sJIA monocytes to IFN may be dysregulated. We examined intracellular signaling in response to IFN type I (IFNα) and type II (IFNγ) in monocytes during sJIA activity and quiescence, in 2 patient groups. Independent of disease activity, monocytes from Group 1 (collected between 2002 and 2009) showed defective STAT1 phosphorylation downstream of IFNs, and expressed higher transcript levels of SOCS1, an inhibitor of IFN signaling. In the Group 2 (collected between 2011 and 2014), monocytes of patients with recent disease onset were IFNγ hyporesponsive, but in treated, quiescent subjects, monocytes were hyperresponsive to IFNγ. Recent changes in medication in sJIA may alter the IFN hyporesponsiveness. Impaired IFN/pSTAT1 signaling is consistent with skewing of sJIA monocytes away from an M1 phenotype and may contribute to disease pathology.
authors.affiliation: Department of Pediatrics, Program in Immunology, Stanford University, Stanford, CA, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Macaubas
authors.affiliation: Department of Pediatrics, Program in Immunology, Stanford University, Stanford, CA, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Wong
authors.affiliation: Department of Pediatrics, Program in Immunology, Stanford University, Stanford, CA, USA.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Program in Immunology, Stanford University, Stanford, CA, USA.
authors.forename: Khoa D
authors.initials: KD
authors.lastname: Nguyen
authors.affiliation: Department of Pediatrics, Program in Immunology, Stanford University, Stanford, CA, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Milojevic
authors.affiliation: Department of Pediatrics, Seattle Children's Hospital & University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Shenoi
authors.affiliation: Department of Pediatrics, Seattle Children's Hospital & University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Stevens
authors.affiliation: Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Norman
authors.initials: N
authors.lastname: Ilowite
authors.affiliation: Department of Pediatrics, Program in Immunology, Stanford University, Stanford, CA, USA.
authors.forename: Vivian
authors.initials: V
authors.lastname: Saper
authors.affiliation: Department of Pediatrics, Program in Immunology, Stanford University, Stanford, CA, USA.
authors.forename: Tzielan
authors.initials: T
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Program in Immunology, Stanford University, Stanford, CA, USA. Electronic address: mellins@stanford.edu.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Mellins
mesh_terms: D000293:Adolescent; D001171:Arthritis, Juvenile / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C108944:SOCS1 protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D007371:Interferon-gamma; D007372:Interferons
keywords: IFN signaling; Juvenile arthritis; Monocytes; SOCS1