TNFSF15 may play an important role in modulating the innate and adaptive immune response.2,3

Binding of TNFSF15 to its receptor, DR3, costimulates lymphocyte proliferation and production of cytokines, such as IFNy.2,3

Preliminary evidence suggests a potential role for TNFSF15 and DR3 inflammatory bowel disease.4,5
• Human genome studies have identified variants in TNFSF15 that may correlate with increased inflammatory bowel disease risk4
• In biopsied tissue, subjects with ulcerative colitis have increased expression of both TNFSF15 and DR35

PF-06480605 is under investigation in moderate to severe ulcerative colitis.6

TNFSF15 PATHWAY

The TNF superfamily member ligand TNFSF15 is associated with the expression of proinflammatory cytokines. Increased levels of TNFSF15 have also been found at the site of inflammation in inflammatory bowel disease. Therefore, inhibition of TNFSF15 may be an option for this condition.2,5

Figure adapted from Richard AC et al. J Leukoc Biol. 2015;98(3):333-345.

  • Members of the tumor necrosis factor (TNF) superfamily are contributors to important immune functions, including inflammation, cell death, homeostasis, host defense, and autoimmunity8
  • The TNF superfamily member 15 (TNFSF15) is a cytokine whose expression is locally induced by proinflammatory stimuli2,5
  • Expression of TNFSF15 has been shown to be upregulated and localized to specific intestinal tissues in subjects with inflammatory bowel disease5
  • TNFSF15 may potentially contribute to inflammatory bowel disease pathology through:
    • Increasing the production of additional proinflammatory cytokines9
    • Mediating mucosal hyperplasia2,10
    • Promoting intestinal fibrosis11,12
  • Genetic variants of TNFSF15 have been associated with the development or susceptibility to autoimmune and inflammatory diseases in certain ethnic populations4,13-17