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

• Published in: Frontiers in immunology 2023-04, Vol.14, p.1021824-1021824
• Main Authors: Andrews, Caroline, McLean, Mairi H, Hixon, Julie A, Pontejo, Sergio M, Starr, Tregei, Malo, Courtney, Cam, Margaret, Ridnour, Lisa, Hickman, Heather, Steele-Mortimer, Olivia, Wink, David A, Young, Howard A, McVicar, Daniel W, Li, Wenqing, Durum, Scott K
• Format: Article
• Language: English
• Subjects: Animals; Colon; colonoid; Epithelium; IBD - inflammatory bowel disease; IFN signature; IL-27 cytokine; Immunology; Inflammatory Bowel Diseases - drug therapy; Interleukin-27 - therapeutic use; Macrophages; Mice
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1021824

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 and to lack detectable IL-27 receptors. On the other hand, macrophages, which are present in inflamed colon tissue, were responsive to IL-27 . 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.