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

Research output: Contribution to journalArticle

50 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
Externally publishedYes

Fingerprint

Fc Receptors
Interleukin-10
Ligation
Rheumatoid Arthritis
Antigen-Antibody Complex
Interferons
Interleukin-10 Receptors
Macrophages
Protein Kinase C-delta
Inflammation
Tissue Transplantation
Macrophage Activation
Homologous Transplantation
Myeloid Cells
Communicable Diseases
Signal Transduction
Joints
Cytokines

Keywords

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

ASJC Scopus subject areas

  • Immunology

Cite this

Ji, J. D., Tassiulas, I., Park-Min, K. H., Aydin, A., Mecklenbräuker, I., Tarakhovsky, A., ... 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

Inhibition of interleukin 10 signaling after Fc receptor ligation and during rheumatoid arthritis. / Ji, Jong Dae; Tassiulas, Ioannis; Park-Min, Kyung Hyun; Aydin, Ani; Mecklenbräuker, Ingrid; Tarakhovsky, Alexander; Pricop, Luminita; Salmon, Jane E.; Ivashkiv, Lionel B.

In: Journal of Experimental Medicine, Vol. 197, No. 11, 02.06.2003, p. 1573-1583.

Research output: Contribution to journalArticle

Ji, JD, Tassiulas, I, Park-Min, KH, Aydin, A, Mecklenbräuker, I, Tarakhovsky, A, Pricop, L, Salmon, JE & Ivashkiv, LB 2003, 'Inhibition of interleukin 10 signaling after Fc receptor ligation and during rheumatoid arthritis', Journal of Experimental Medicine, vol. 197, no. 11, pp. 1573-1583. https://doi.org/10.1084/jem.20021820
Ji, Jong Dae ; Tassiulas, Ioannis ; Park-Min, Kyung Hyun ; Aydin, Ani ; Mecklenbräuker, Ingrid ; Tarakhovsky, Alexander ; Pricop, Luminita ; Salmon, Jane E. ; Ivashkiv, Lionel B. / Inhibition of interleukin 10 signaling after Fc receptor ligation and during rheumatoid arthritis. In: Journal of Experimental Medicine. 2003 ; Vol. 197, No. 11. pp. 1573-1583.
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