ST2 requires Th2-, but not Th17-, type airway inflammation in epicutaneously antigen-sensitized mice

Hideaki Morita, Ken Arae, Tatsukuni Ohno, Naoki Kajiwara, Keisuke Oboki, Akio Matsuda, Hajime Suto, Ko Okumura, Katsuko Sudo, Takao Takahashi, Kenji Matsumoto, Susumu Nakae

Research output: Contribution to journalArticle

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Abstract

Background: IL-33 is known to induce Th2-type cytokine production by various types of cells through its receptors, ST2 and IL-1RAcP. Polymorphism in the ST2 and/or IL-33 genes was found in patients with atopic dermatitis and asthma, implying that the IL-33/ST2 pathway is closely associated with susceptibility to these diseases. Exposure to allergens through damaged skin is suspected to be a trigger for allergen sensitization, resulting in development of such allergic disorders as asthma and atopic dermatitis. Methods: To elucidate the role(s) of the IL-33/ST2 pathway in asthma in individuals who had been epicutaneously sensitized to an antigen, wild-type and ST2-/- mice were epicutaneously sensitized with ovalbumin (OVA) and then were intranasally challenged with OVA. The degree of airway inflammation, the number of leukocytes and the activities of myeloperoxidase (MPO) and eosinophil peroxidase (EPO) in bronchoalveolar lavage fluids (BALFs), The levels of cytokines and chemokines in lungs and OVA-specific IgE levels in sera were determined by histological analysis, a hemocytometer, colorimetric assay, quantitative PCR or ELISA, respectively. Results: The number of eosinophils in BALFs, the levels of Th2 cytokines and chemoattractants in the lungs and OVA-specific IgE in sera from ST2-/- mice were significantly reduced compared with wild-type mice. Although the number of neutrophils in BALFs and the pulmonary levels of IL-17 were comparable in both mice, the levels of MPO activity in BALFs and neutrophil chemoattractants in the lung were reduced in ST2-/- mice. Conclusions: The IL-33/ST2 pathway is crucial for Th2-cytokine-mediated eosinophilic, rather than Th17-cytokine-mediated neutrophilic, airway inflammation in mice that had been epicutaneously sensitized with antigens and then challenged with antigen.

Original languageEnglish
Pages (from-to)265-273
Number of pages9
JournalAllergology International
Volume61
Issue number2
DOIs
Publication statusPublished - 2012

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Ovalbumin
Bronchoalveolar Lavage Fluid
Inflammation
Antigens
Cytokines
Lung
Chemotactic Factors
Allergens
Immunoglobulin E
Peroxidase
Interleukin-1 Receptor Accessory Protein
Neutrophils
Asthma
Eosinophil Peroxidase
Interleukin-17
Disease Susceptibility
Atopic Dermatitis
Serum
Leukocyte Count
Chemokines

Keywords

  • Asthma
  • Eosinophils
  • Epicutaneous sensitization
  • IL-33
  • ST2

ASJC Scopus subject areas

  • Immunology and Allergy

Cite this

ST2 requires Th2-, but not Th17-, type airway inflammation in epicutaneously antigen-sensitized mice. / Morita, Hideaki; Arae, Ken; Ohno, Tatsukuni; Kajiwara, Naoki; Oboki, Keisuke; Matsuda, Akio; Suto, Hajime; Okumura, Ko; Sudo, Katsuko; Takahashi, Takao; Matsumoto, Kenji; Nakae, Susumu.

In: Allergology International, Vol. 61, No. 2, 2012, p. 265-273.

Research output: Contribution to journalArticle

Morita, H, Arae, K, Ohno, T, Kajiwara, N, Oboki, K, Matsuda, A, Suto, H, Okumura, K, Sudo, K, Takahashi, T, Matsumoto, K & Nakae, S 2012, 'ST2 requires Th2-, but not Th17-, type airway inflammation in epicutaneously antigen-sensitized mice', Allergology International, vol. 61, no. 2, pp. 265-273. https://doi.org/10.2332/allergolint.11-OA-0379
Morita, Hideaki ; Arae, Ken ; Ohno, Tatsukuni ; Kajiwara, Naoki ; Oboki, Keisuke ; Matsuda, Akio ; Suto, Hajime ; Okumura, Ko ; Sudo, Katsuko ; Takahashi, Takao ; Matsumoto, Kenji ; Nakae, Susumu. / ST2 requires Th2-, but not Th17-, type airway inflammation in epicutaneously antigen-sensitized mice. In: Allergology International. 2012 ; Vol. 61, No. 2. pp. 265-273.
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abstract = "Background: IL-33 is known to induce Th2-type cytokine production by various types of cells through its receptors, ST2 and IL-1RAcP. Polymorphism in the ST2 and/or IL-33 genes was found in patients with atopic dermatitis and asthma, implying that the IL-33/ST2 pathway is closely associated with susceptibility to these diseases. Exposure to allergens through damaged skin is suspected to be a trigger for allergen sensitization, resulting in development of such allergic disorders as asthma and atopic dermatitis. Methods: To elucidate the role(s) of the IL-33/ST2 pathway in asthma in individuals who had been epicutaneously sensitized to an antigen, wild-type and ST2-/- mice were epicutaneously sensitized with ovalbumin (OVA) and then were intranasally challenged with OVA. The degree of airway inflammation, the number of leukocytes and the activities of myeloperoxidase (MPO) and eosinophil peroxidase (EPO) in bronchoalveolar lavage fluids (BALFs), The levels of cytokines and chemokines in lungs and OVA-specific IgE levels in sera were determined by histological analysis, a hemocytometer, colorimetric assay, quantitative PCR or ELISA, respectively. Results: The number of eosinophils in BALFs, the levels of Th2 cytokines and chemoattractants in the lungs and OVA-specific IgE in sera from ST2-/- mice were significantly reduced compared with wild-type mice. Although the number of neutrophils in BALFs and the pulmonary levels of IL-17 were comparable in both mice, the levels of MPO activity in BALFs and neutrophil chemoattractants in the lung were reduced in ST2-/- mice. Conclusions: The IL-33/ST2 pathway is crucial for Th2-cytokine-mediated eosinophilic, rather than Th17-cytokine-mediated neutrophilic, airway inflammation in mice that had been epicutaneously sensitized with antigens and then challenged with antigen.",
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T1 - ST2 requires Th2-, but not Th17-, type airway inflammation in epicutaneously antigen-sensitized mice

AU - Morita, Hideaki

AU - Arae, Ken

AU - Ohno, Tatsukuni

AU - Kajiwara, Naoki

AU - Oboki, Keisuke

AU - Matsuda, Akio

AU - Suto, Hajime

AU - Okumura, Ko

AU - Sudo, Katsuko

AU - Takahashi, Takao

AU - Matsumoto, Kenji

AU - Nakae, Susumu

PY - 2012

Y1 - 2012

N2 - Background: IL-33 is known to induce Th2-type cytokine production by various types of cells through its receptors, ST2 and IL-1RAcP. Polymorphism in the ST2 and/or IL-33 genes was found in patients with atopic dermatitis and asthma, implying that the IL-33/ST2 pathway is closely associated with susceptibility to these diseases. Exposure to allergens through damaged skin is suspected to be a trigger for allergen sensitization, resulting in development of such allergic disorders as asthma and atopic dermatitis. Methods: To elucidate the role(s) of the IL-33/ST2 pathway in asthma in individuals who had been epicutaneously sensitized to an antigen, wild-type and ST2-/- mice were epicutaneously sensitized with ovalbumin (OVA) and then were intranasally challenged with OVA. The degree of airway inflammation, the number of leukocytes and the activities of myeloperoxidase (MPO) and eosinophil peroxidase (EPO) in bronchoalveolar lavage fluids (BALFs), The levels of cytokines and chemokines in lungs and OVA-specific IgE levels in sera were determined by histological analysis, a hemocytometer, colorimetric assay, quantitative PCR or ELISA, respectively. Results: The number of eosinophils in BALFs, the levels of Th2 cytokines and chemoattractants in the lungs and OVA-specific IgE in sera from ST2-/- mice were significantly reduced compared with wild-type mice. Although the number of neutrophils in BALFs and the pulmonary levels of IL-17 were comparable in both mice, the levels of MPO activity in BALFs and neutrophil chemoattractants in the lung were reduced in ST2-/- mice. Conclusions: The IL-33/ST2 pathway is crucial for Th2-cytokine-mediated eosinophilic, rather than Th17-cytokine-mediated neutrophilic, airway inflammation in mice that had been epicutaneously sensitized with antigens and then challenged with antigen.

AB - Background: IL-33 is known to induce Th2-type cytokine production by various types of cells through its receptors, ST2 and IL-1RAcP. Polymorphism in the ST2 and/or IL-33 genes was found in patients with atopic dermatitis and asthma, implying that the IL-33/ST2 pathway is closely associated with susceptibility to these diseases. Exposure to allergens through damaged skin is suspected to be a trigger for allergen sensitization, resulting in development of such allergic disorders as asthma and atopic dermatitis. Methods: To elucidate the role(s) of the IL-33/ST2 pathway in asthma in individuals who had been epicutaneously sensitized to an antigen, wild-type and ST2-/- mice were epicutaneously sensitized with ovalbumin (OVA) and then were intranasally challenged with OVA. The degree of airway inflammation, the number of leukocytes and the activities of myeloperoxidase (MPO) and eosinophil peroxidase (EPO) in bronchoalveolar lavage fluids (BALFs), The levels of cytokines and chemokines in lungs and OVA-specific IgE levels in sera were determined by histological analysis, a hemocytometer, colorimetric assay, quantitative PCR or ELISA, respectively. Results: The number of eosinophils in BALFs, the levels of Th2 cytokines and chemoattractants in the lungs and OVA-specific IgE in sera from ST2-/- mice were significantly reduced compared with wild-type mice. Although the number of neutrophils in BALFs and the pulmonary levels of IL-17 were comparable in both mice, the levels of MPO activity in BALFs and neutrophil chemoattractants in the lung were reduced in ST2-/- mice. Conclusions: The IL-33/ST2 pathway is crucial for Th2-cytokine-mediated eosinophilic, rather than Th17-cytokine-mediated neutrophilic, airway inflammation in mice that had been epicutaneously sensitized with antigens and then challenged with antigen.

KW - Asthma

KW - Eosinophils

KW - Epicutaneous sensitization

KW - IL-33

KW - ST2

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