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Nat Med. 2017 May;23(5):579-589. doi: 10.1038/nm.4307. Epub 2017 Apr 3.

Oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor-neutralizing therapy in patients with inflammatory bowel disease.

Author information

Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Somerville College, University of Oxford, Oxford, UK.
Janssen Research and Development, Raritan, New Jersey, USA.
Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Institute of Biochemistry and Molecular Biology, RWTH Aachen University, Aachen, Germany.
Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Charité-Universitätsmedizin Berlin, Germany.
OPPF-UK, The Research Complex at Harwell, Rutherford Appleton Laboratory, Harwell, Oxford, UK.
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.


Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex chronic inflammatory conditions of the gastrointestinal tract that are driven by perturbed cytokine pathways. Anti-tumor necrosis factor-α (TNF) antibodies are mainstay therapies for IBD. However, up to 40% of patients are nonresponsive to anti-TNF agents, which makes the identification of alternative therapeutic targets a priority. Here we show that, relative to healthy controls, inflamed intestinal tissues from patients with IBD express high amounts of the cytokine oncostatin M (OSM) and its receptor (OSMR), which correlate closely with histopathological disease severity. The OSMR is expressed in nonhematopoietic, nonepithelial intestinal stromal cells, which respond to OSM by producing various proinflammatory molecules, including interleukin (IL)-6, the leukocyte adhesion factor ICAM1, and chemokines that attract neutrophils, monocytes, and T cells. In an animal model of anti-TNF-resistant intestinal inflammation, genetic deletion or pharmacological blockade of OSM significantly attenuates colitis. Furthermore, according to an analysis of more than 200 patients with IBD, including two cohorts from phase 3 clinical trials of infliximab and golimumab, high pretreatment expression of OSM is strongly associated with failure of anti-TNF therapy. OSM is thus a potential biomarker and therapeutic target for IBD, and has particular relevance for anti-TNF-resistant patients.

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