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Differential activation of airway eosinophils induces IL ‐13‐mediated allergic Th2 pulmonary responses in mice
Author(s) -
Jacobsen E. A.,
Doyle A. D.,
Colbert D. C.,
Zellner K. R.,
Protheroe C. A.,
LeSuer W. E.,
Lee N. A.,
Lee J. J.
Publication year - 2015
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12655
Subject(s) - immunology , eosinophil , cytokine , medicine , interleukin 5 , allergic inflammation , immune system , inflammation , interleukin , asthma
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 CD 4 + T cells to these same LDLN s 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 CD 4 + 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.