Interleukin-27 Is a Potential Rescue Therapy for Acute Severe Colitis Through Interleukin-10–Dependent, T-Cell–Independent Attenuation of Colonic Mucosal Innate Immune Responses

Mairi H. McLean, Caroline Andrews, Miranda L. Hanson, Walter A. Baseler, Miriam R. Anver, Emilee Senkevitch, Aleksandra K. Staniszewska , Luke C. Davies, Julie Hixon, Wenqeng Li, Wei Shen, Lothar Steidler, Scott K. Durum

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18 Citations (Scopus)
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Background; IBD patients with acute severe colitis face systemic anti-TNF biologic rescue therapy or colectomy, if treatment with intravenous steroids fail. Interleukin (IL)-27 is a cytokine with an immunosuppressive role in adaptive immune responses. However, the IL-27 receptor complex is also expressed on innate immune cells, and there is evidence that IL-27 can impact the function of innate cell subsets, although this particular functionality in vivo is not understood. Our aim was to define the efficacy of IL-27 in acute severe colitis and characterize novel IL-27 driven mechanisms of immunosuppression in the colonic mucosa.

Methods; We assessed oral delivery of Lactococcus lactis expressing an IL-27 hyperkine on the innate immune response in vivo in a genetically intact, non-infective acute murine colitis model induced by intra-rectal instillation of 2,4,6-Trinitrobenzenesulfonic acid in SJL/J mice.

Results; IL-27 attenuates acute severe colitis through reduction of colonic mucosal neutrophil infiltrate associated with a decreased CXC chemokine gradient. This suppression was T cell-independent and IL- 10-dependent, initially featuring enhanced mucosal IL-10. IL-27 was associated with a reduction in colonic pro-inflammatory cytokines and induced a multifocal strong positive nuclear expression of phosphorylated STAT-1 in mucosal epithelial cells.

Conclusion; We have defined novel mechanisms of IL-27 immunosuppression towards colonic innate immune responses in vivo. Mucosal delivery of IL-27 has translational potential as a novel therapeutic for IBD and is a future mucosal directed rescue therapy in acute severe inflammatory bowel disease.
Original languageEnglish
Pages (from-to)1983-1995
Number of pages12
JournalInflammatory Bowel Diseases
Issue number11
Early online date9 Oct 2017
Publication statusPublished - Nov 2017

Bibliographical note

This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, as well as a fellowship funded by Crohn’s and Colitis Foundation of America (MHM) and a grant from the Broad Medical Research Foundation. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E (MRA). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.


  • interleukin-27
  • cytokine
  • IBD
  • colitis


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