@article{7ade4027de95460988227d311c769c1f,
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.",
keywords = "IFN signaling, Juvenile arthritis, Monocytes, SOCS1",
author = "Claudia Macaubas and Elizabeth Wong and Yujuan Zhang and Nguyen, {Khoa D.} and Justin Lee and Diana Milojevic and Susan Shenoi and Stevens, {Anne M.} and Norman Ilowite and Vivian Saper and Tzielan Lee and Mellins, {Elizabeth D.}",
note = "Funding Information: We would like to thank the patients, their families and the medical and nursing staff of the Pediatric Rheumatology and Pediatric Endocrinology Clinics at Stanford Children{\textquoteright}s Health, University of California San Francisco and Seattle Children's Hospital & University of Washington School of Medicine. We thank Virginia Pascual (Baylor Institute for Immunology Research, TX) for providing monocyte RNA from a subset of RAPPORT samples. We also thank Yael Gernez, Jacob Dorn, Ariana Peck, Jane L. Park, Carolyn Phillips, Isaac Alter and Rebecca Kunder (Stanford University, CA) for the help with sample collection, and flow cytometry and RT-PCR experiments. Supported by the Wasie Foundation , the Dana Foundation , the Child Health Research Program of Stanford University , the National Institutes of Health (NIH R01AR061297 ) (to EM), the Becton Dickinson Immunology Grant (to CM), and the Thrasher Foundation (to SS). The funding agencies had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2016",
month = feb,
day = "1",
doi = "10.1016/j.clim.2015.12.011",
language = "English (US)",
volume = "163",
pages = "66--74",
journal = "Clinical Immunology",
issn = "1521-6616",
publisher = "Academic Press Inc.",
}