Peptidoglycan recognition protein 1 enhances experimental asthma by promoting Th2 and Th17 and limiting regulatory T cell and plasmacytoid dendritic cell responses

Shin Yong Park, Xuefang Jing, Dipika Gupta, Roman Dziarski

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Abstract

Asthma is a common inflammatory disease involving cross-talk between innate and adaptive immunity.We reveal that antibacterial innate immunity protein, peptidoglycan recognition protein (Pglyrp)1, is involved in the development of allergic asthma. Pglyrp1-/- mice developed less severe asthma than wild-type (WT) mice following sensitization with house dust mite (allergen) (HDM). HDMsensitized Pglyrp1-/- mice, compared with WT mice, had diminished bronchial hyperresponsiveness (lung airway resistance); numbers of eosinophils, neutrophils, lymphocytes, and macrophages in bronchoalveolar lavage fluid and lungs; inflammatory cell infiltrates in the lungs around bronchi, bronchioles, and pulmonary arteries and veins; lung remodeling (mucin-producing goblet cell hyperplasia and metaplasia and smooth muscle hypertrophy and fibrosis); levels of IgE, eotaxins, IL-4, IL-5, and IL-17 in the lungs; and numbers of Th2 and Th17 cells and expression of their marker genes in the lungs. The mechanism underlying this decreased sensitivity of Pglyrp1-/- mice to asthma was increased generation and activation of CD8α +β+ and CD8α+β- plasmacytoid dendritic cells (pDC) and increased recruitment and activity of regulatory T (Treg) cells in the lungs. In vivo depletion of pDC in HDM-sensitized Pglyrp1-/- mice reversed the low responsive asthma phenotype of Pglyrp1-/- mice to resemble the more severe WT phenotype. Thus, Pglyrp1-/- mice efficiently control allergic asthma by upregulating pDC and Treg cells in the lungs, whereas in WT mice, Pglyrp1 is proinflammatory and decreases pDC and Treg cells and increases proasthmatic Th2 and Th17 responses. Blocking Pglyrp1 or enhancing pDC in the lungs may be beneficial for prevention and treatment of asthma. Copyright

Original languageEnglish
Pages (from-to)3480-3492
Number of pages13
JournalJournal of Immunology
Volume190
Issue number7
DOIs
StatePublished - Apr 1 2013

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Regulatory T-Lymphocytes
Dendritic Cells
Asthma
Lung
Innate Immunity
Personnel Selection
Dermatophagoides Antigens
Bronchioles
Phenotype
peptidoglycan recognition protein
Th17 Cells
Th2 Cells
Airway Resistance
Goblet Cells
Interleukin-17
Pulmonary Veins
Interleukin-5
Bronchoalveolar Lavage Fluid
Metaplasia
Adaptive Immunity

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "Peptidoglycan recognition protein 1 enhances experimental asthma by promoting Th2 and Th17 and limiting regulatory T cell and plasmacytoid dendritic cell responses",
abstract = "Asthma is a common inflammatory disease involving cross-talk between innate and adaptive immunity.We reveal that antibacterial innate immunity protein, peptidoglycan recognition protein (Pglyrp)1, is involved in the development of allergic asthma. Pglyrp1-/- mice developed less severe asthma than wild-type (WT) mice following sensitization with house dust mite (allergen) (HDM). HDMsensitized Pglyrp1-/- mice, compared with WT mice, had diminished bronchial hyperresponsiveness (lung airway resistance); numbers of eosinophils, neutrophils, lymphocytes, and macrophages in bronchoalveolar lavage fluid and lungs; inflammatory cell infiltrates in the lungs around bronchi, bronchioles, and pulmonary arteries and veins; lung remodeling (mucin-producing goblet cell hyperplasia and metaplasia and smooth muscle hypertrophy and fibrosis); levels of IgE, eotaxins, IL-4, IL-5, and IL-17 in the lungs; and numbers of Th2 and Th17 cells and expression of their marker genes in the lungs. The mechanism underlying this decreased sensitivity of Pglyrp1-/- mice to asthma was increased generation and activation of CD8α +β+ and CD8α+β- plasmacytoid dendritic cells (pDC) and increased recruitment and activity of regulatory T (Treg) cells in the lungs. In vivo depletion of pDC in HDM-sensitized Pglyrp1-/- mice reversed the low responsive asthma phenotype of Pglyrp1-/- mice to resemble the more severe WT phenotype. Thus, Pglyrp1-/- mice efficiently control allergic asthma by upregulating pDC and Treg cells in the lungs, whereas in WT mice, Pglyrp1 is proinflammatory and decreases pDC and Treg cells and increases proasthmatic Th2 and Th17 responses. Blocking Pglyrp1 or enhancing pDC in the lungs may be beneficial for prevention and treatment of asthma. Copyright",
author = "Park, {Shin Yong} and Xuefang Jing and Dipika Gupta and Roman Dziarski",
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T1 - Peptidoglycan recognition protein 1 enhances experimental asthma by promoting Th2 and Th17 and limiting regulatory T cell and plasmacytoid dendritic cell responses

AU - Park, Shin Yong

AU - Jing, Xuefang

AU - Gupta, Dipika

AU - Dziarski, Roman

PY - 2013/4/1

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N2 - Asthma is a common inflammatory disease involving cross-talk between innate and adaptive immunity.We reveal that antibacterial innate immunity protein, peptidoglycan recognition protein (Pglyrp)1, is involved in the development of allergic asthma. Pglyrp1-/- mice developed less severe asthma than wild-type (WT) mice following sensitization with house dust mite (allergen) (HDM). HDMsensitized Pglyrp1-/- mice, compared with WT mice, had diminished bronchial hyperresponsiveness (lung airway resistance); numbers of eosinophils, neutrophils, lymphocytes, and macrophages in bronchoalveolar lavage fluid and lungs; inflammatory cell infiltrates in the lungs around bronchi, bronchioles, and pulmonary arteries and veins; lung remodeling (mucin-producing goblet cell hyperplasia and metaplasia and smooth muscle hypertrophy and fibrosis); levels of IgE, eotaxins, IL-4, IL-5, and IL-17 in the lungs; and numbers of Th2 and Th17 cells and expression of their marker genes in the lungs. The mechanism underlying this decreased sensitivity of Pglyrp1-/- mice to asthma was increased generation and activation of CD8α +β+ and CD8α+β- plasmacytoid dendritic cells (pDC) and increased recruitment and activity of regulatory T (Treg) cells in the lungs. In vivo depletion of pDC in HDM-sensitized Pglyrp1-/- mice reversed the low responsive asthma phenotype of Pglyrp1-/- mice to resemble the more severe WT phenotype. Thus, Pglyrp1-/- mice efficiently control allergic asthma by upregulating pDC and Treg cells in the lungs, whereas in WT mice, Pglyrp1 is proinflammatory and decreases pDC and Treg cells and increases proasthmatic Th2 and Th17 responses. Blocking Pglyrp1 or enhancing pDC in the lungs may be beneficial for prevention and treatment of asthma. Copyright

AB - Asthma is a common inflammatory disease involving cross-talk between innate and adaptive immunity.We reveal that antibacterial innate immunity protein, peptidoglycan recognition protein (Pglyrp)1, is involved in the development of allergic asthma. Pglyrp1-/- mice developed less severe asthma than wild-type (WT) mice following sensitization with house dust mite (allergen) (HDM). HDMsensitized Pglyrp1-/- mice, compared with WT mice, had diminished bronchial hyperresponsiveness (lung airway resistance); numbers of eosinophils, neutrophils, lymphocytes, and macrophages in bronchoalveolar lavage fluid and lungs; inflammatory cell infiltrates in the lungs around bronchi, bronchioles, and pulmonary arteries and veins; lung remodeling (mucin-producing goblet cell hyperplasia and metaplasia and smooth muscle hypertrophy and fibrosis); levels of IgE, eotaxins, IL-4, IL-5, and IL-17 in the lungs; and numbers of Th2 and Th17 cells and expression of their marker genes in the lungs. The mechanism underlying this decreased sensitivity of Pglyrp1-/- mice to asthma was increased generation and activation of CD8α +β+ and CD8α+β- plasmacytoid dendritic cells (pDC) and increased recruitment and activity of regulatory T (Treg) cells in the lungs. In vivo depletion of pDC in HDM-sensitized Pglyrp1-/- mice reversed the low responsive asthma phenotype of Pglyrp1-/- mice to resemble the more severe WT phenotype. Thus, Pglyrp1-/- mice efficiently control allergic asthma by upregulating pDC and Treg cells in the lungs, whereas in WT mice, Pglyrp1 is proinflammatory and decreases pDC and Treg cells and increases proasthmatic Th2 and Th17 responses. Blocking Pglyrp1 or enhancing pDC in the lungs may be beneficial for prevention and treatment of asthma. Copyright

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