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

Journal article

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-tumour necrosis factor-α (TNF) antibodies are a mainstay therapeutic approach for IBD. However, up to 40% of patients are non-responsive to anti-TNF agents, and identifying alternative therapeutic targets is a priority. Here we show that expression of the cytokine Oncostatin M (OSM) and its receptor (OSMR) is increased in the inflamed intestine of IBD patients compared to healthy controls, and correlates closely with histopathological disease severity. OSMR is expressed in non-hematopoietic, non-epithelial intestinal stromal cells, which respond to OSM by producing various pro-inflammatory factors including interleukin-6 (IL-6), the leukocyte adhesion factor ICAM-1, and chemokines that attract neutrophils, monocytes, and T cells. In an animal model of anti-TNF refractory intestinal inflammation, genetic deletion or pharmacological blockade of OSM significantly attenuates colitis. Furthermore, high pre-treatment OSM expression is strongly associated with failure of anti-TNF therapy based on analysis of over 200 IBD patients, including two cohorts from phase 3 clinical trials of infliximab and golimumab. OSM is thus a potential biomarker and therapeutic target for IBD, with particular relevance for anti-TNF refractory patients.

Authors: West, N; Hegazy, A; Owens, B; Bullers, S; Linggi, B

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Publishing Group
• Journal: Nature Medicine
• Volume: 23
• Pages: 579–589
• Publication date: 2017-04-01
• Acceptance date: 2017-02-17
• DOI: 10.1038/nm.4307
• EISSN: 1546-170X
• ISSN: 1078-8956
• Language: English
• Keywords: Journal Article