Published online Nov 12, 2018. doi: 10.4291/wjgp.v9.i4.73
Peer-review started: August 3, 2018
First decision: August 30, 2018
Revised: October 11, 2018
Accepted: October 17, 2018
Article in press: October 18, 2018
Published online: November 12, 2018
Processing time: 101 Days and 10.9 Hours
Gastrointestinal diseases, specifically Crohn’s disease, ulcerative colitis, diverticular disease, and primary biliary cirrhosis are all characterized by complicated inflammation of the digestive tract. Their pathology is multifactorial, and risk factors encompass both genetic and environmental factors. Recent advances in the genetic component of inflammatory bowel diseases (IBDs) have revealed that the tumor necrosis factor superfamily member 15 (TNFSF15) contains a number of risk alleles associated not only with IBD but also with other diseases such as diverticular disease and primary biliary cirrhosis. These risk alleles in TNFSF15 and the altered expression of its gene product can serve as the common ground between these disorders by explaining at least some of the underlying processes that lead to a dysregulated immune response and subsequent chronic inflammation. Here, we aim to outline how the TNFSF15 gene is involved in the proliferation and cell fate of different populations of T cells and subsequently in the control of both pro- and anti-inflammatory cytokines. Furthermore, we summarize what is currently known of TNFSF15 control region variants, how they are associated with each mentioned disease, and how these variants can explain the autoimmune pathology of said diseases through altered TNFSF15 expression.
Core tip: Tumor necrosis factor superfamily member 15 and the protein it encodes, tumor necrosis factor ligand-related molecule 1 play a vital role in the mucosal immunity. Expression of tumor necrosis factor ligand-related molecule 1 and death receptor 3-mediated signaling both exert their effects in Crohn’s disease, ulcerative colitis, diverticular disease, and primary biliary cirrhosis, which can serve to bridge the gap of knowledge regarding the genetic components of this group of inflammatory diseases as well as provide common ground for a putative targeted treatment.