Altered signaling in systemic juvenile idiopathic arthritis monocytes

Claudia Macaubas, Elizabeth Wong, Yujuan Zhang, Khoa D. Nguyen, Justin Lee, Diana Milojevic, Susan Shenoi, Anne M. Stevens, Norman Todd Ilowite, Vivian Saper, Tzielan Lee, Elizabeth D. Mellins

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)66-74
Number of pages9
JournalClinical Immunology
Volume163
DOIs
StatePublished - Feb 1 2016

    Fingerprint

Keywords

  • IFN signaling
  • Juvenile arthritis
  • Monocytes
  • SOCS1

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Macaubas, C., Wong, E., Zhang, Y., Nguyen, K. D., Lee, J., Milojevic, D., Shenoi, S., Stevens, A. M., Ilowite, N. T., Saper, V., Lee, T., & Mellins, E. D. (2016). Altered signaling in systemic juvenile idiopathic arthritis monocytes. Clinical Immunology, 163, 66-74. https://doi.org/10.1016/j.clim.2015.12.011