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

Biochim Biophys Acta Mol Basis Dis. 2020 Dec 1;1866(12):165950. doi: 10.1016/j.bbadis.2020.165950. Epub 2020 Aug 22.

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.

Keywords: Airway inflammation; IL-33; Lungs; STAT4; Transcriptome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Female
  • Interleukin-33 / administration & dosage
  • Interleukin-33 / immunology*
  • Lung / immunology*
  • Lung / metabolism*
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Models, Animal*
  • RNA-Seq
  • Transcriptome*

Substances

  • Il33 protein, mouse
  • Interleukin-33