The tumor necrosis factor family member TNFSF14 (LIGHT) is required for resolution of intestinal inflammation in mice

Gastroenterology. 2014 Jun;146(7):1752-62.e4. doi: 10.1053/j.gastro.2014.02.010. Epub 2014 Feb 19.


Background & aims: The pathogenesis of inflammatory bowel disease (IBD) is associated with a dysregulated mucosal immune response. Expression of the tumor necrosis factor (TNF) superfamily member 14 (TNFSF14, also known as LIGHT [homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes]) on T cells is involved in their activation; transgenic expression of LIGHT on T cells in mice promotes inflammation in multiple organs, including intestine. We investigated the roles for LIGHT in recovery from intestinal inflammation in mice.

Methods: We studied the role of LIGHT in intestinal inflammation using Tnfsf14(-/-) and wild-type mice. Colitis was induced by transfer of CD4(+)CD45RB(high) T cells into Rag1(-/-) or Tnfsf14(-/-)Rag1(-/-) mice, or by administration of dextran sulfate sodium to Tnfsf14(-/-) or wild-type C57BL/6J mice. Mice were weighed, colon tissues were collected and measured, and histology analyses were performed. We measured infiltrating cell populations and expression of cytokines, chemokines, and LIGHT.

Results: After administration of dextran sulfate sodium, Tnfsf14(-/-) mice developed more severe colitis than controls, based on their reduced survival, accelerated loss of body weight, and histologic scores. LIGHT protected mice from colitis via the lymphotoxin β receptor and was expressed mainly by myeloid cells in the colon. Colons of Tnfsf14(-/-) mice also had increased accumulation of innate immune cells and higher levels of cytokines than colons from control mice. LIGHT, therefore, appears to regulate inflammation in the colon.

Conclusions: Tnfsf14(-/-) mice develop more severe colitis than control mice. LIGHT signals through the lymphotoxin β receptor in the colon to regulate the innate immune response and mediate recovery from intestinal inflammation.

Keywords: IBD; Innate Immunity; Mouse Model; Ulcerative Colitis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / transplantation
  • Colitis / chemically induced
  • Colitis / immunology
  • Colitis / metabolism*
  • Colitis / pathology
  • Colitis / prevention & control
  • Colon / immunology
  • Colon / metabolism*
  • Colon / pathology
  • Cytokines / metabolism
  • Dextran Sulfate
  • Disease Models, Animal
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Immunity, Innate
  • Inflammation Mediators / metabolism
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / pathology
  • Leukocyte Common Antigens / metabolism
  • Lymphotoxin beta Receptor / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Severity of Illness Index
  • Signal Transduction
  • Time Factors
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / deficiency
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / genetics
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / metabolism*
  • Weight Loss


  • Cytokines
  • Homeodomain Proteins
  • Inflammation Mediators
  • Ltbr protein, mouse
  • Lymphotoxin beta Receptor
  • Tnfsf14 protein, mouse
  • Tumor Necrosis Factor Ligand Superfamily Member 14
  • RAG-1 protein
  • Dextran Sulfate
  • Leukocyte Common Antigens
  • PTPRC protein, human