Inhibition of interleukin 10 signaling after Fc receptor ligation and during rheumatoid arthritis

Jong Dae Ji, Ioannis Tassiulas, Kyung Hyun Park-Min, Ani Aydin, Ingrid Mecklenbräuker, Alexander Tarakhovsky, Luminita Pricop, Jane E. Salmon, Lionel B. Ivashkiv

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52 Citations (Scopus)

Abstract

Interleukin-10 (IL-10) is a potent deactivator of myeloid cells that limits the intensity and duration of immune and inflammatory responses. The activity of IL-10 can be suppressed during inflammation, infection, or after allogeneic tissue transplantation. We investigated whether inflammatory factors suppress IL-10 activity at the level of signal transduction. Out of many factors tested, only ligation of Fc receptors by immune complexes inhibited IL-10 activation of the Jak-Stat signaling pathway. IL-10 signaling was suppressed in rheumatoid arthritis joint macrophages that are exposed to immune complexes in vivo. Activation of macrophages with interferon-γ was required for Fc receptor-mediated suppression of IL-10 signaling, which resulted in diminished activation of IL-10-inducible genes and reversal of IL-10-dependent suppression of cytokine production. The mechanism of inhibition involved decreased cell surface IL-10 receptor expression and Jak1 activation and was dependent on protein kinase C delta. These results establish that IL-10 signaling is regulated during inflammation and identify Fc receptors and interferon-γ as important regulators of IL-10 activity. Generation of macrophages refractory to IL-10 can contribute to pathogenesis of inflammatory and infectious diseases characterized by production of interferon-γ and immune complexes.

Original languageEnglish
Pages (from-to)1573-1583
Number of pages11
JournalJournal of Experimental Medicine
Volume197
Issue number11
DOIs
Publication statusPublished - 2003 Jun 2

Keywords

  • Fc receptor
  • Interleukin 10
  • Jak-Stat
  • Macrophage
  • Signal transduction

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Ji, J. D., Tassiulas, I., Park-Min, K. H., Aydin, A., Mecklenbräuker, I., Tarakhovsky, A., Pricop, L., Salmon, J. E., & Ivashkiv, L. B. (2003). Inhibition of interleukin 10 signaling after Fc receptor ligation and during rheumatoid arthritis. Journal of Experimental Medicine, 197(11), 1573-1583. https://doi.org/10.1084/jem.20021820