Differential activation of airway eosinophils induces IL-13-mediated allergic Th2 pulmonary responses in mice

Elizabeth Jacobsen, A. D. Doyle, D. C. Colbert, K. R. Zellner, C. A. Protheroe, W. E. Lesuer, Nancy A Lee, J. J. Lee

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background Eosinophils are hallmark cells of allergic Th2 respiratory inflammation. However, the relative importance of eosinophil activation and the induction of effector functions such as the expression of IL-13 to allergic Th2 pulmonary disease remain to be defined. Methods Wild-type or cytokine-deficient (IL-13<sup>-/-</sup> or IL-4<sup>-/-</sup>) eosinophils treated with cytokines (GM-CSF, IL-4, IL-33) were adoptively transferred into eosinophil-deficient recipient mice subjected to allergen provocation using established models of respiratory inflammation. Allergen-induced pulmonary changes were assessed. Results In contrast to the transfer of untreated blood eosinophils to the lungs of recipient eosinophil deficient mice, which induced no immune/inflammatory changes either in the lung or in the lung draining lymph nodes (LDLN), pretreatment of blood eosinophils with GM-CSF prior to transfer elicited trafficking of these eosinophils to LDLN. In turn, these LDLN eosinophils elicited the accumulation of dendritic cells and CD4<sup>+</sup> T cells to these same LDLNs without inducing pulmonary inflammation. However, exposure of eosinophils to GM-CSF, IL-4, and IL-33 prior to transfer induced not only immune events in the LDLN, but also allergen-mediated increases in airway Th2 cytokine/chemokine levels, the subsequent accumulation of CD4<sup>+</sup> T cells as well as alternatively activated (M2) macrophages, and the induction of pulmonary histopathologies. Significantly, this allergic respiratory inflammation was dependent on eosinophil-derived IL-13, whereas IL-4 expression by eosinophils had no significant role. Conclusion The data demonstrate the differential activation of eosinophils as a function of cytokine exposure and suggest that eosinophil-specific IL-13 expression by activated cells is a necessary component of the subsequent allergic Th2 pulmonary pathologies.

Original languageEnglish (US)
Pages (from-to)1148-1159
Number of pages12
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume70
Issue number9
DOIs
StatePublished - Sep 1 2015

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Interleukin-13
Eosinophils
Lung
Interleukin-4
Granulocyte-Macrophage Colony-Stimulating Factor
Lymph Nodes
Allergens
Cytokines
Inflammation
T-Lymphocytes
Th2 Cells
Alveolar Macrophages
Chemokines
Dendritic Cells
Lung Diseases
Pneumonia

Keywords

  • Asthma
  • Eosinophil deficient
  • IL-13
  • IL-33
  • T cells

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Differential activation of airway eosinophils induces IL-13-mediated allergic Th2 pulmonary responses in mice. / Jacobsen, Elizabeth; Doyle, A. D.; Colbert, D. C.; Zellner, K. R.; Protheroe, C. A.; Lesuer, W. E.; Lee, Nancy A; Lee, J. J.

In: Allergy: European Journal of Allergy and Clinical Immunology, Vol. 70, No. 9, 01.09.2015, p. 1148-1159.

Research output: Contribution to journalArticle

Jacobsen, Elizabeth ; Doyle, A. D. ; Colbert, D. C. ; Zellner, K. R. ; Protheroe, C. A. ; Lesuer, W. E. ; Lee, Nancy A ; Lee, J. J. / Differential activation of airway eosinophils induces IL-13-mediated allergic Th2 pulmonary responses in mice. In: Allergy: European Journal of Allergy and Clinical Immunology. 2015 ; Vol. 70, No. 9. pp. 1148-1159.
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abstract = "Background Eosinophils are hallmark cells of allergic Th2 respiratory inflammation. However, the relative importance of eosinophil activation and the induction of effector functions such as the expression of IL-13 to allergic Th2 pulmonary disease remain to be defined. Methods Wild-type or cytokine-deficient (IL-13-/- or IL-4-/-) eosinophils treated with cytokines (GM-CSF, IL-4, IL-33) were adoptively transferred into eosinophil-deficient recipient mice subjected to allergen provocation using established models of respiratory inflammation. Allergen-induced pulmonary changes were assessed. Results In contrast to the transfer of untreated blood eosinophils to the lungs of recipient eosinophil deficient mice, which induced no immune/inflammatory changes either in the lung or in the lung draining lymph nodes (LDLN), pretreatment of blood eosinophils with GM-CSF prior to transfer elicited trafficking of these eosinophils to LDLN. In turn, these LDLN eosinophils elicited the accumulation of dendritic cells and CD4+ T cells to these same LDLNs without inducing pulmonary inflammation. However, exposure of eosinophils to GM-CSF, IL-4, and IL-33 prior to transfer induced not only immune events in the LDLN, but also allergen-mediated increases in airway Th2 cytokine/chemokine levels, the subsequent accumulation of CD4+ T cells as well as alternatively activated (M2) macrophages, and the induction of pulmonary histopathologies. Significantly, this allergic respiratory inflammation was dependent on eosinophil-derived IL-13, whereas IL-4 expression by eosinophils had no significant role. Conclusion The data demonstrate the differential activation of eosinophils as a function of cytokine exposure and suggest that eosinophil-specific IL-13 expression by activated cells is a necessary component of the subsequent allergic Th2 pulmonary pathologies.",
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T1 - Differential activation of airway eosinophils induces IL-13-mediated allergic Th2 pulmonary responses in mice

AU - Jacobsen, Elizabeth

AU - Doyle, A. D.

AU - Colbert, D. C.

AU - Zellner, K. R.

AU - Protheroe, C. A.

AU - Lesuer, W. E.

AU - Lee, Nancy A

AU - Lee, J. J.

PY - 2015/9/1

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N2 - Background Eosinophils are hallmark cells of allergic Th2 respiratory inflammation. However, the relative importance of eosinophil activation and the induction of effector functions such as the expression of IL-13 to allergic Th2 pulmonary disease remain to be defined. Methods Wild-type or cytokine-deficient (IL-13-/- or IL-4-/-) eosinophils treated with cytokines (GM-CSF, IL-4, IL-33) were adoptively transferred into eosinophil-deficient recipient mice subjected to allergen provocation using established models of respiratory inflammation. Allergen-induced pulmonary changes were assessed. Results In contrast to the transfer of untreated blood eosinophils to the lungs of recipient eosinophil deficient mice, which induced no immune/inflammatory changes either in the lung or in the lung draining lymph nodes (LDLN), pretreatment of blood eosinophils with GM-CSF prior to transfer elicited trafficking of these eosinophils to LDLN. In turn, these LDLN eosinophils elicited the accumulation of dendritic cells and CD4+ T cells to these same LDLNs without inducing pulmonary inflammation. However, exposure of eosinophils to GM-CSF, IL-4, and IL-33 prior to transfer induced not only immune events in the LDLN, but also allergen-mediated increases in airway Th2 cytokine/chemokine levels, the subsequent accumulation of CD4+ T cells as well as alternatively activated (M2) macrophages, and the induction of pulmonary histopathologies. Significantly, this allergic respiratory inflammation was dependent on eosinophil-derived IL-13, whereas IL-4 expression by eosinophils had no significant role. Conclusion The data demonstrate the differential activation of eosinophils as a function of cytokine exposure and suggest that eosinophil-specific IL-13 expression by activated cells is a necessary component of the subsequent allergic Th2 pulmonary pathologies.

AB - Background Eosinophils are hallmark cells of allergic Th2 respiratory inflammation. However, the relative importance of eosinophil activation and the induction of effector functions such as the expression of IL-13 to allergic Th2 pulmonary disease remain to be defined. Methods Wild-type or cytokine-deficient (IL-13-/- or IL-4-/-) eosinophils treated with cytokines (GM-CSF, IL-4, IL-33) were adoptively transferred into eosinophil-deficient recipient mice subjected to allergen provocation using established models of respiratory inflammation. Allergen-induced pulmonary changes were assessed. Results In contrast to the transfer of untreated blood eosinophils to the lungs of recipient eosinophil deficient mice, which induced no immune/inflammatory changes either in the lung or in the lung draining lymph nodes (LDLN), pretreatment of blood eosinophils with GM-CSF prior to transfer elicited trafficking of these eosinophils to LDLN. In turn, these LDLN eosinophils elicited the accumulation of dendritic cells and CD4+ T cells to these same LDLNs without inducing pulmonary inflammation. However, exposure of eosinophils to GM-CSF, IL-4, and IL-33 prior to transfer induced not only immune events in the LDLN, but also allergen-mediated increases in airway Th2 cytokine/chemokine levels, the subsequent accumulation of CD4+ T cells as well as alternatively activated (M2) macrophages, and the induction of pulmonary histopathologies. Significantly, this allergic respiratory inflammation was dependent on eosinophil-derived IL-13, whereas IL-4 expression by eosinophils had no significant role. Conclusion The data demonstrate the differential activation of eosinophils as a function of cytokine exposure and suggest that eosinophil-specific IL-13 expression by activated cells is a necessary component of the subsequent allergic Th2 pulmonary pathologies.

KW - Asthma

KW - Eosinophil deficient

KW - IL-13

KW - IL-33

KW - T cells

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