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

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


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.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Case-Control Studies
  • Chemokines
  • Colitis / genetics
  • Colitis / immunology
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Gastrointestinal Agents / therapeutic use
  • Gene Expression Profiling
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Inflammation
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / genetics*
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / metabolism
  • Infliximab / therapeutic use
  • Intercellular Adhesion Molecule-1 / immunology
  • Interleukin-6 / immunology
  • Male
  • Mice
  • Mice, Knockout
  • Middle Aged
  • Oncostatin M / genetics*
  • Oncostatin M / immunology
  • Oncostatin M / metabolism
  • Oncostatin M Receptor beta Subunit / genetics*
  • Oncostatin M Receptor beta Subunit / immunology
  • Oncostatin M Receptor beta Subunit / metabolism
  • Real-Time Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Young Adult


  • Antibodies, Monoclonal
  • Chemokines
  • Gastrointestinal Agents
  • IL6 protein, human
  • Interleukin-6
  • OSM protein, human
  • OSMR protein, human
  • Oncostatin M Receptor beta Subunit
  • Osm protein, mouse
  • Osmr protein, mouse
  • Tumor Necrosis Factor-alpha
  • Oncostatin M
  • Intercellular Adhesion Molecule-1
  • golimumab
  • Infliximab