title: The tumor necrosis factor family member TNFSF14 (LIGHT) is required for resolution of intestinal inflammation in mice.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy & Immunology, La Jolla, California.
authors.forename: Petra
authors.initials: P
authors.lastname: Krause
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy & Immunology, La Jolla, California.
authors.forename: Sonja P
authors.initials: SP
authors.lastname: Zahner
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy & Immunology, La Jolla, California.
authors.forename: Gisen
authors.initials: G
authors.lastname: Kim
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy & Immunology, La Jolla, California.
authors.forename: Raziyah B
authors.initials: RB
authors.lastname: Shaikh
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy & Immunology, La Jolla, California.
authors.forename: Marcos W
authors.initials: MW
authors.lastname: Steinberg
authors.affiliation: Division of Developmental Immunology, La Jolla Institute for Allergy & Immunology, La Jolla, California. Electronic address: mitch@liai.org.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kronenberg
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D003106:Colon / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D053259:Lymphotoxin beta Receptor / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012720:Severity of Illness Index; D015398:Signal Transduction; D013997:Time Factors; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015431:Weight Loss
chemical_list: D016207:Cytokines; D018398:Homeodomain Proteins; D018836:Inflammation Mediators; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; C064658:RAG-1 protein; D016264:Dextran Sulfate; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human
keywords: IBD; Innate Immunity; Mouse Model; Ulcerative Colitis