IL-27 induces an IFN-like signature in murine macrophages which in turn modulate colonic epithelium

Caroline Andrews, Mairi H. McLean, Julie A. Hixon, Sergio M. Pontejo, Tregei Starr, Courtney Malo, Margaret Cam, Lisa Ridnour, Heather Hickman, Olivia Steele-Mortimer, David A. Wink, Howard A. Young, Daniel W. McVicar, Wenqing Li, Scott K. Durum (Lead / Corresponding author)

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1 Citation (Scopus)
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Abstract

Mucosal delivery of IL-27 has been shown to have a therapeutic benefit in murine models of inflammatory bowel disease (IBD). The IL-27 effect was associated with phosphorylated STAT1 (pSTAT1), a product of IL27 receptor signaling, in bowel tissue. To determine whether IL-27 acted directly on colonic epithelium, murine colonoids and primary intact colonic crypts were shown to be unresponsive to IL-27 in vitro and to lack detectable IL-27 receptors. On the other hand, macrophages, which are present in inflamed colon tissue, were responsive to IL-27 in vitro. IL-27 induced pSTAT1 in macrophages, the transcriptome indicated an IFN-like signature, and supernatants induced pSTAT1 in colonoids. IL-27 induced anti-viral activity in macrophages and MHC Class II induction. We conclude that the effects of mucosal delivery of IL-27 in murine IBD are in part based on the known effects of IL27 inducing immunosuppression of T cells mediated by IL-10. We also conclude that IL-27 has potent effects on macrophages in inflamed colon tissue, generating mediators that in turn act on colonic epithelium.

Original languageEnglish
Article number1021824
Number of pages9
JournalFrontiers in Immunology
Volume14
DOIs
Publication statusPublished - 20 Apr 2023

Keywords

  • Mice
  • Animals
  • Interleukin-27/therapeutic use
  • Colon
  • Inflammatory Bowel Diseases/drug therapy
  • Macrophages
  • Epithelium
  • IL-27 cytokine
  • macrophages
  • IFN signature
  • IBD - inflammatory bowel disease
  • colonoid

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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