Early life represents a vulnerable time window for IL-33–induced peripheral lung pathology

Li Y. Drake, Diane Squillace, Koji Iijima, Takao Kobayashi, Masaru Uchida, Gail M. Kephart, Rodney Britt, Daniel R. O’Brien, Hirohito Kita

Research output: Contribution to journalArticle

Abstract

IL-33, an IL-1 family cytokine, is constitutively expressed in mucosal tissues and other organs in healthy humans and animals, and expression levels increase in inflammatory conditions. Although IL-33–mediated promotion of type 2 immune responses has been well established, a gap in our knowledge regarding the functional diversity of this pleiotropic cytokine remains. To address this gap, we developed a new IL-33 transgenic mouse model in which overexpression of full-length IL-33 is induced in lung epithelial cells under conditional control. In adult mice, an ∼3-fold increase in the steady-state IL-33 levels produced no pathologic effects in the lungs. When exposed to airborne allergens, adult transgenic mice released more IL-33 extracellularly and exhibited robust type 2 immune responses. In neonatal transgenic mice, up to postnatal day 14, a similar increase in steady-state IL-33 levels resulted in increased mortality, enlarged alveolar spaces resembling bronchopulmonary dysplasia, and altered expression of genes associated with tissue morphogenesis. Processed 25-kDa IL-33 protein was detected in bronchoalveolar lavage fluids without any exogenous stimuli, and pathologic changes were abolished in mice deficient in the IL-33 receptor ST2. These findings suggest that adult lungs are relatively resistant to IL-33 overexpression unless they encounter environmental insults, whereas developing lungs are highly susceptible, with IL-33 overexpression resulting in detrimental and pathologic outcomes.

Original languageEnglish (US)
Pages (from-to)1952-1960
Number of pages9
JournalJournal of Immunology
Volume203
Issue number7
DOIs
StatePublished - Oct 1 2019

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Pathology
Lung
Transgenic Mice
Interleukin-33
Cytokines
Bronchopulmonary Dysplasia
Bronchoalveolar Lavage Fluid
Interleukin-1
Morphogenesis
Allergens
Mucous Membrane
Epithelial Cells
Gene Expression
Mortality
Proteins

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Drake, L. Y., Squillace, D., Iijima, K., Kobayashi, T., Uchida, M., Kephart, G. M., ... Kita, H. (2019). Early life represents a vulnerable time window for IL-33–induced peripheral lung pathology. Journal of Immunology, 203(7), 1952-1960. https://doi.org/10.4049/jimmunol.1900454

Early life represents a vulnerable time window for IL-33–induced peripheral lung pathology. / Drake, Li Y.; Squillace, Diane; Iijima, Koji; Kobayashi, Takao; Uchida, Masaru; Kephart, Gail M.; Britt, Rodney; O’Brien, Daniel R.; Kita, Hirohito.

In: Journal of Immunology, Vol. 203, No. 7, 01.10.2019, p. 1952-1960.

Research output: Contribution to journalArticle

Drake, LY, Squillace, D, Iijima, K, Kobayashi, T, Uchida, M, Kephart, GM, Britt, R, O’Brien, DR & Kita, H 2019, 'Early life represents a vulnerable time window for IL-33–induced peripheral lung pathology', Journal of Immunology, vol. 203, no. 7, pp. 1952-1960. https://doi.org/10.4049/jimmunol.1900454
Drake LY, Squillace D, Iijima K, Kobayashi T, Uchida M, Kephart GM et al. Early life represents a vulnerable time window for IL-33–induced peripheral lung pathology. Journal of Immunology. 2019 Oct 1;203(7):1952-1960. https://doi.org/10.4049/jimmunol.1900454
Drake, Li Y. ; Squillace, Diane ; Iijima, Koji ; Kobayashi, Takao ; Uchida, Masaru ; Kephart, Gail M. ; Britt, Rodney ; O’Brien, Daniel R. ; Kita, Hirohito. / Early life represents a vulnerable time window for IL-33–induced peripheral lung pathology. In: Journal of Immunology. 2019 ; Vol. 203, No. 7. pp. 1952-1960.
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