title: Dysregulated LIGHT expression on T cells mediates intestinal inflammation and contributes to IgA nephropathy.
abstract: Whether and how T cells contribute to the pathogenesis of immunoglobulin A nephropathy (IgAN) has not been well defined. Here, we explore a murine model that spontaneously develops T cell-mediated intestinal inflammation accompanied by pathological features similar to those of human IgAN. Intestinal inflammation mediated by LIGHT, a ligand for lymphotoxin beta receptor (LTbetaR), not only stimulates IgA overproduction in the gut but also results in defective IgA transportation into the gut lumen, causing a dramatic increase in serum polymeric IgA. Engagement of LTbetaR by LIGHT is essential for both intestinal inflammation and hyperserum IgA syndrome in our LIGHT transgenic model. Impressively, the majority of patients with inflammatory bowel disease showed increased IgA-producing cells in the gut, elevated serum IgA levels, and severe hematuria, a hallmark of IgAN. These observations indicate the critical contributions of dysregulated LIGHT expression and intestinal inflammation to the pathogenesis of IgAN.
authors.affiliation: Department of Pathology, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Robert A
authors.initials: RA
authors.lastname: Anders
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.forename: Dacheng
authors.initials: D
authors.lastname: Peng
authors.forename: Judy H
authors.initials: JH
authors.lastname: Cho
authors.forename: Yonglian
authors.initials: Y
authors.lastname: Sun
authors.forename: Reda
authors.initials: R
authors.lastname: Karaliukas
authors.forename: Hyung-Sik
authors.initials: HS
authors.lastname: Kang
authors.forename: Jerrold R
authors.initials: JR
authors.lastname: Turner
authors.forename: Yang-Xin
authors.initials: YX
authors.lastname: Fu
mesh_terms: D000818:Animals; D003176:Complement C3 / Q000378:metabolism; D005759:Gastroenteritis / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology / Q000502:physiology*; D005922:Glomerulonephritis, IGA / Q000276:immunology*; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000378:metabolism; D007678:Kidney Glomerulus / Q000276:immunology; D053259:Lymphotoxin beta Receptor; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D003176:Complement C3; D007070:Immunoglobulin A; C505697:LTBR protein, human; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; C505914:TNFSF14 protein, human; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha