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

Author:

Andrews, Caroline

McLean, Mairi H

Hixon,Julie

Pontejo, Sergio M

Starr, Tregei

Malo, Courtney

Cam, Margaret

Ridnour, Lisa

Hickman, Heather

Steele-Mortimer, Olivia

Wink,David

Young,Howard

McVicar,Daniel

Li,Wenqing

Durum,Scott
Author Address

Laboratory of Cancer Innovation, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, United States., Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, United Kingdom., Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States., Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, United States., Viral Immunity and Pathogenesis Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States., Center for Cancer Research Collaborative Bioinformatics Resource, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.,

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. Copyright © 2023 Andrews, McLean, Hixon, Pontejo, Starr, Malo, Cam, Ridnour, Hickman, Steele-Mortimer, Wink, Young, McVicar, Li and Durum.

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