AUTHOR=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. TITLE=IL-27 induces an IFN-like signature in murine macrophages which in turn modulate colonic epithelium JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1021824 DOI=10.3389/fimmu.2023.1021824 ISSN=1664-3224 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.