Interferons modulate FcεRI-dependent production of autoregulatory IL-10 by circulating human monocytoid dendritic cells

Trong Le, Jody Tversky, Kristin L. Chichester, Anja P. Bieneman, Shau Ku Huang, Robert A. Wood, John T. Schroeder

Research output: Contribution to journalArticle

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Abstract

Background: Immature human blood monocytoid dendritic cells (mDCs) express high-affinity receptors for IgE (FcεRI), yet their exact function and regulation remain poorly understood. Objective: We sought to characterize FcεRI-dependent cytokine responses and their regulation in circulating human blood mDCs. Methods: FcεRI-dependent cytokine responses of circulating mDCs were studied by using anti-FcεRIα stimulation. Plasmacytoid dendritic cell (pDC) cross-regulation through Toll-like receptor 9 on these responses was investigated by examining the effects of exogenous IFN-α pretreatment and by coculturing pDCs and mDCs stimulated with CpG. Culture supernatants were analyzed by means of ELISA to determine cytokine levels. Cell markers were determined by means of flow cytometry. Results: mDCs express marked levels of FcεRI (net mean fluorescence intensity, 196 ± 49; n = 4). After FcεRI-dependent activation in mDCs, TNF-α (2189 ± 864 pg/106 mDCs, n = 3) levels were upregulated within 4 hours, whereas IL-10 (112 ± 47 pg/106 mDCs, n = 3) levels were detectable only after 24 hours of incubation. After adding IL-10-neutralizing antibody, TNF-α FcεRI-dependent responses were significantly augmented (3903 ± 197 pg/106 mDCs, P < .01, n = 3). Conversely, recombinant IL-10 dose-dependently inhibited FcεRI-mediated TNF-α responses up to 86% ± 3% (n = 3, P < .001). Pretreatment of mDCs with IFN-α (100 U/mL) enhanced FcεRI-dependent secretion of IL-10 by 3.2-fold (183 ± 11 pg/106 mDCs, n = 4) compared with that seen in untreated cells (57 ± 33 pg/106 mDCs, P < .001, n = 4). In pDC/mDC cocultures pretreated with CpG, FcεRI-dependent IL-10 secretion by mDCs was similarly augmented by 3-fold. Conclusions: Autocrine secretion of IL-10, a critical autoregulator of FcεRI-dependent proinflammatory responses in mDCs, is cross-regulated by IFN-α, a major product of Toll-like receptor 9 responses in pDCs that normally promotes TH1 immunity.

Original languageEnglish
Pages (from-to)217-223
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume123
Issue number1
DOIs
Publication statusPublished - Jan 1 2009
Externally publishedYes

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Interleukin-10
Dendritic Cells
Interferons
Toll-Like Receptor 9
Cytokines
IgE Receptors
Coculture Techniques
Neutralizing Antibodies
Immunity
Flow Cytometry
Fluorescence

Keywords

  • Dendritic cells
  • FcεRI
  • IFN-α
  • IL-10
  • TNF-α

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Interferons modulate FcεRI-dependent production of autoregulatory IL-10 by circulating human monocytoid dendritic cells. / Le, Trong; Tversky, Jody; Chichester, Kristin L.; Bieneman, Anja P.; Huang, Shau Ku; Wood, Robert A.; Schroeder, John T.

In: Journal of Allergy and Clinical Immunology, Vol. 123, No. 1, 01.01.2009, p. 217-223.

Research output: Contribution to journalArticle

Le, Trong ; Tversky, Jody ; Chichester, Kristin L. ; Bieneman, Anja P. ; Huang, Shau Ku ; Wood, Robert A. ; Schroeder, John T. / Interferons modulate FcεRI-dependent production of autoregulatory IL-10 by circulating human monocytoid dendritic cells. In: Journal of Allergy and Clinical Immunology. 2009 ; Vol. 123, No. 1. pp. 217-223.
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AU - Le, Trong

AU - Tversky, Jody

AU - Chichester, Kristin L.

AU - Bieneman, Anja P.

AU - Huang, Shau Ku

AU - Wood, Robert A.

AU - Schroeder, John T.

PY - 2009/1/1

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N2 - Background: Immature human blood monocytoid dendritic cells (mDCs) express high-affinity receptors for IgE (FcεRI), yet their exact function and regulation remain poorly understood. Objective: We sought to characterize FcεRI-dependent cytokine responses and their regulation in circulating human blood mDCs. Methods: FcεRI-dependent cytokine responses of circulating mDCs were studied by using anti-FcεRIα stimulation. Plasmacytoid dendritic cell (pDC) cross-regulation through Toll-like receptor 9 on these responses was investigated by examining the effects of exogenous IFN-α pretreatment and by coculturing pDCs and mDCs stimulated with CpG. Culture supernatants were analyzed by means of ELISA to determine cytokine levels. Cell markers were determined by means of flow cytometry. Results: mDCs express marked levels of FcεRI (net mean fluorescence intensity, 196 ± 49; n = 4). After FcεRI-dependent activation in mDCs, TNF-α (2189 ± 864 pg/106 mDCs, n = 3) levels were upregulated within 4 hours, whereas IL-10 (112 ± 47 pg/106 mDCs, n = 3) levels were detectable only after 24 hours of incubation. After adding IL-10-neutralizing antibody, TNF-α FcεRI-dependent responses were significantly augmented (3903 ± 197 pg/106 mDCs, P < .01, n = 3). Conversely, recombinant IL-10 dose-dependently inhibited FcεRI-mediated TNF-α responses up to 86% ± 3% (n = 3, P < .001). Pretreatment of mDCs with IFN-α (100 U/mL) enhanced FcεRI-dependent secretion of IL-10 by 3.2-fold (183 ± 11 pg/106 mDCs, n = 4) compared with that seen in untreated cells (57 ± 33 pg/106 mDCs, P < .001, n = 4). In pDC/mDC cocultures pretreated with CpG, FcεRI-dependent IL-10 secretion by mDCs was similarly augmented by 3-fold. Conclusions: Autocrine secretion of IL-10, a critical autoregulator of FcεRI-dependent proinflammatory responses in mDCs, is cross-regulated by IFN-α, a major product of Toll-like receptor 9 responses in pDCs that normally promotes TH1 immunity.

AB - Background: Immature human blood monocytoid dendritic cells (mDCs) express high-affinity receptors for IgE (FcεRI), yet their exact function and regulation remain poorly understood. Objective: We sought to characterize FcεRI-dependent cytokine responses and their regulation in circulating human blood mDCs. Methods: FcεRI-dependent cytokine responses of circulating mDCs were studied by using anti-FcεRIα stimulation. Plasmacytoid dendritic cell (pDC) cross-regulation through Toll-like receptor 9 on these responses was investigated by examining the effects of exogenous IFN-α pretreatment and by coculturing pDCs and mDCs stimulated with CpG. Culture supernatants were analyzed by means of ELISA to determine cytokine levels. Cell markers were determined by means of flow cytometry. Results: mDCs express marked levels of FcεRI (net mean fluorescence intensity, 196 ± 49; n = 4). After FcεRI-dependent activation in mDCs, TNF-α (2189 ± 864 pg/106 mDCs, n = 3) levels were upregulated within 4 hours, whereas IL-10 (112 ± 47 pg/106 mDCs, n = 3) levels were detectable only after 24 hours of incubation. After adding IL-10-neutralizing antibody, TNF-α FcεRI-dependent responses were significantly augmented (3903 ± 197 pg/106 mDCs, P < .01, n = 3). Conversely, recombinant IL-10 dose-dependently inhibited FcεRI-mediated TNF-α responses up to 86% ± 3% (n = 3, P < .001). Pretreatment of mDCs with IFN-α (100 U/mL) enhanced FcεRI-dependent secretion of IL-10 by 3.2-fold (183 ± 11 pg/106 mDCs, n = 4) compared with that seen in untreated cells (57 ± 33 pg/106 mDCs, P < .001, n = 4). In pDC/mDC cocultures pretreated with CpG, FcεRI-dependent IL-10 secretion by mDCs was similarly augmented by 3-fold. Conclusions: Autocrine secretion of IL-10, a critical autoregulator of FcεRI-dependent proinflammatory responses in mDCs, is cross-regulated by IFN-α, a major product of Toll-like receptor 9 responses in pDCs that normally promotes TH1 immunity.

KW - Dendritic cells

KW - FcεRI

KW - IFN-α

KW - IL-10

KW - TNF-α

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