IL-10-treated dendritic cells decrease airway hyperresponsiveness and airway inflammation in mice

Toshiyuki Koya, Hiroyuki Matsuda, Katsuyuki Takeda, Shigeki Matsubara, Nobuaki Miyahara, Annette Balhorn, Azzeddine Dakhama, Erwin W. Gelfand

Research output: Contribution to journalArticle

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Abstract

Background: IL-10 affects dendritic cell (DC) function, but the effects on airway hyperresponsiveness (AHR) and inflammation are not defined. Objective: We sought to determine the importance of IL-10 in regulating DC function in allergen-induced AHR and airway inflammation. Methods: DCs were generated from bone marrow in the presence or absence of IL-10. In vivo IL-10-treated DCs from IL-10 +/+ and IL-10 -/- donors pulsed with ovalbumin (OVA) were transferred to naive or sensitized mice before challenge. In recipient mice AHR, cytokine levels, cell composition of bronchoalveolar lavage (BAL) fluid, and lung histology were monitored. Results: In vitro, IL-10-treated DCs expressed lower levels of CD11c, CD80, and CD86; expressed lower levels of IL-12; and suppressed T H2 cytokine production. In vivo, after transfer of OVA-pulsed IL-10-treated DCs, naive mice did not have AHR, airway eosinophilia, T H2 cytokine increase in BAL fluid, or goblet cell metaplasia when challenged, and in sensitized and challenged mice IL-10-treated DCs suppressed these responses. Levels of IL-10 in BAL fluid and numbers of lung CD4 +IL-10 + T cells were increased in mice that received OVA-pulsed IL-10-treated DCs. Transfer of IL-10-treated DCs from IL-10-deficient mice were ineffective in suppressing the responses in sensitized and challenged mice. Conclusions: These data demonstrate that IL-10-treated DCs are potent suppressors of the development of AHR, inflammation, and T H2 cytokine production; these regulatory functions are at least in part through the induction of endogenous (DC) production of IL-10. Clinical implications: Modification of DC function by IL-10 can attenuate lung allergic responses, including the development of AHR.

Original languageEnglish
Pages (from-to)1241-1250
Number of pages10
JournalJournal of Allergy and Clinical Immunology
Volume119
Issue number5
DOIs
Publication statusPublished - May 2007
Externally publishedYes

Fingerprint

Interleukin-10
Dendritic Cells
Inflammation
Ovalbumin
Bronchoalveolar Lavage Fluid
Cytokines
Lung
Goblet Cells
Metaplasia
Eosinophilia
Interleukin-12
Allergens
Histology

Keywords

  • airway hyperresponsiveness
  • eosinophils
  • IL-10-treated dendritic cells
  • regulatory T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

IL-10-treated dendritic cells decrease airway hyperresponsiveness and airway inflammation in mice. / Koya, Toshiyuki; Matsuda, Hiroyuki; Takeda, Katsuyuki; Matsubara, Shigeki; Miyahara, Nobuaki; Balhorn, Annette; Dakhama, Azzeddine; Gelfand, Erwin W.

In: Journal of Allergy and Clinical Immunology, Vol. 119, No. 5, 05.2007, p. 1241-1250.

Research output: Contribution to journalArticle

Koya, Toshiyuki ; Matsuda, Hiroyuki ; Takeda, Katsuyuki ; Matsubara, Shigeki ; Miyahara, Nobuaki ; Balhorn, Annette ; Dakhama, Azzeddine ; Gelfand, Erwin W. / IL-10-treated dendritic cells decrease airway hyperresponsiveness and airway inflammation in mice. In: Journal of Allergy and Clinical Immunology. 2007 ; Vol. 119, No. 5. pp. 1241-1250.
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AU - Koya, Toshiyuki

AU - Matsuda, Hiroyuki

AU - Takeda, Katsuyuki

AU - Matsubara, Shigeki

AU - Miyahara, Nobuaki

AU - Balhorn, Annette

AU - Dakhama, Azzeddine

AU - Gelfand, Erwin W.

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AB - Background: IL-10 affects dendritic cell (DC) function, but the effects on airway hyperresponsiveness (AHR) and inflammation are not defined. Objective: We sought to determine the importance of IL-10 in regulating DC function in allergen-induced AHR and airway inflammation. Methods: DCs were generated from bone marrow in the presence or absence of IL-10. In vivo IL-10-treated DCs from IL-10 +/+ and IL-10 -/- donors pulsed with ovalbumin (OVA) were transferred to naive or sensitized mice before challenge. In recipient mice AHR, cytokine levels, cell composition of bronchoalveolar lavage (BAL) fluid, and lung histology were monitored. Results: In vitro, IL-10-treated DCs expressed lower levels of CD11c, CD80, and CD86; expressed lower levels of IL-12; and suppressed T H2 cytokine production. In vivo, after transfer of OVA-pulsed IL-10-treated DCs, naive mice did not have AHR, airway eosinophilia, T H2 cytokine increase in BAL fluid, or goblet cell metaplasia when challenged, and in sensitized and challenged mice IL-10-treated DCs suppressed these responses. Levels of IL-10 in BAL fluid and numbers of lung CD4 +IL-10 + T cells were increased in mice that received OVA-pulsed IL-10-treated DCs. Transfer of IL-10-treated DCs from IL-10-deficient mice were ineffective in suppressing the responses in sensitized and challenged mice. Conclusions: These data demonstrate that IL-10-treated DCs are potent suppressors of the development of AHR, inflammation, and T H2 cytokine production; these regulatory functions are at least in part through the induction of endogenous (DC) production of IL-10. Clinical implications: Modification of DC function by IL-10 can attenuate lung allergic responses, including the development of AHR.

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KW - eosinophils

KW - IL-10-treated dendritic cells

KW - regulatory T cells

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