Inhaled delivery of Interferon-lambda restricts epithelial-derived Th2 inflammation in allergic asthma

Jina Won, Chan Hee Gil, Ara Jo, Hyun Jik Kim

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The possibility has been suggested that interferon (IFN)-λs can be induced rapidly for restricting respiratory viral infection in asthmatic mice and may modulate Th2-related immune responses that underlie the pathogenesis of asthma. We sought to determine the in vivo contribution of IFN-λs on decrease of Th2 cytokines in the respiratory tract of in vivo asthma. Lungs of asthmatic mice were severely inflamed, with extensive inflammatory cell infiltration and increased goblet cell metaplasia with higher total lung resistance. The mean protein levels of TSLP and IL-33 from BAL fluid of asthmatic mice were significantly higher until 7 days. Following the collection of lung tissue of 20 asthmatic mice, TSLP and IL-33 gene expressions inversely correlated with mRNA levels of IFN-λ 2/3 . Asthmatic mice were administered recombinant IFN-λ 2/3 via the intranasal route and the mRNA levels of IFN-stimulated genes were elevated to an even greater extent in the lung tissue of the mice without intranasal IFN-λ 2/3 . Asthma-related histopathologic lung inflammation was significantly improved and total lung resistance was maintained within normal range in IFN-λ 2/3 -treated asthmatic mice. Moreover, IFN-λ 2/3 -treated asthmatic mice exhibited significant decrease of secreted protein levels of TSLP and IL-33 in the BAL fluid until 7 days after IFN administration. The current data provide compelling evidence that the compensation of IFN-λs can restrict the secretion of epithelial-derived Th2 cytokines, accompanied with reduced asthmatic immunopathology and IFN-λs are critical for limiting Th2-mediated allergic responses in allergic asthma.

Original languageEnglish
Pages (from-to)32-36
Number of pages5
JournalCytokine
Volume119
DOIs
StatePublished - 1 Jul 2019

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Interferons
Asthma
Inflammation
Lung
Dimercaprol
Tissue
Cytokines
Messenger RNA
Goblet Cells
Fluids
Metaplasia
Virus Diseases
Infiltration
Gene expression
Respiratory Tract Infections
Respiratory System
Pneumonia
Reference Values
Proteins
Genes

Keywords

  • Asthma
  • IFN-λs
  • Intranasal inhalation
  • Th2 cytokines

Cite this

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abstract = "The possibility has been suggested that interferon (IFN)-λs can be induced rapidly for restricting respiratory viral infection in asthmatic mice and may modulate Th2-related immune responses that underlie the pathogenesis of asthma. We sought to determine the in vivo contribution of IFN-λs on decrease of Th2 cytokines in the respiratory tract of in vivo asthma. Lungs of asthmatic mice were severely inflamed, with extensive inflammatory cell infiltration and increased goblet cell metaplasia with higher total lung resistance. The mean protein levels of TSLP and IL-33 from BAL fluid of asthmatic mice were significantly higher until 7 days. Following the collection of lung tissue of 20 asthmatic mice, TSLP and IL-33 gene expressions inversely correlated with mRNA levels of IFN-λ 2/3 . Asthmatic mice were administered recombinant IFN-λ 2/3 via the intranasal route and the mRNA levels of IFN-stimulated genes were elevated to an even greater extent in the lung tissue of the mice without intranasal IFN-λ 2/3 . Asthma-related histopathologic lung inflammation was significantly improved and total lung resistance was maintained within normal range in IFN-λ 2/3 -treated asthmatic mice. Moreover, IFN-λ 2/3 -treated asthmatic mice exhibited significant decrease of secreted protein levels of TSLP and IL-33 in the BAL fluid until 7 days after IFN administration. The current data provide compelling evidence that the compensation of IFN-λs can restrict the secretion of epithelial-derived Th2 cytokines, accompanied with reduced asthmatic immunopathology and IFN-λs are critical for limiting Th2-mediated allergic responses in allergic asthma.",
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Inhaled delivery of Interferon-lambda restricts epithelial-derived Th2 inflammation in allergic asthma. / Won, Jina; Gil, Chan Hee; Jo, Ara; Kim, Hyun Jik.

In: Cytokine, Vol. 119, 01.07.2019, p. 32-36.

Research output: Contribution to journalArticleResearchpeer-review

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