Characterization of immune responses and the lung transcriptome in a murine model of IL-33 challenge

Hadeesha Piyadasa, Dylan Lloyd, Amy H.Y. Lee, Anthony Altieri, Mahadevappa Hemshekhar, Natasha Osawa, Sujata Basu, Travis Blimkie, Reza Falsafi, Andrew J. Halayko, Robert E.W. Hancock, Neeloffer Mookherjee

Research output: Contribution to journalArticlepeer-review

Abstract

IL-33 induces airway inflammation and hyper-responsiveness in respiratory diseases. Although defined as a therapeutic target, there are limited studies that have comprehensively investigated IL-33-mediated responses in the lungs in vivo. In this study, we characterized immunological and physiological responses induced by intranasal IL-33 challenge, in a mouse model. We identified specific cytokines, IL-4, IL-5, IL-6, IL-10, IP-10 and MIP1-α, that are increased in bronchoalveolar lavage and lung tissues by IL-33. Using transcriptomics (RNA-Seq) we demonstrated that 2279 transcripts were up-regulated and 1378 downregulated (≥ 2-fold, p < 0.01) in lung tissues, in response to IL-33. Bioinformatic interrogation of the RNA-Seq data was used to predict biological pathways and upstream regulators involved in IL-33-mediated responses. We showed that the mRNA and protein of STAT4, a predicted upstream regulator of IL-33-induced transcripts, was significantly enhanced in the lungs following IL-33 challenge. Overall, this study provides specific IL-33-induced molecular targets and endpoints that can be used as a resource for in vivo studies, e.g. in preclinical murine models examining novel interventions to target downstream effects of IL-33.

Original languageEnglish
Article number165950
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1866
Issue number12
DOIs
Publication statusPublished or Issued - 1 Dec 2020

Keywords

  • Airway inflammation
  • IL-33
  • Lungs
  • STAT4
  • Transcriptome

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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