1. IL-27 induces an IFN-like signature in murine macrophages which in turn modulate colonic epithelium
- Author
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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, and Scott K. Durum
- Subjects
IL-27 cytokine ,IBD - inflammatory bowel disease ,macrophages ,IFN signature ,colonoid ,Immunologic diseases. Allergy ,RC581-607 - 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.
- Published
- 2023
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