Dysregulated LIGHT expression on T cells mediates intestinal inflammation and contributes to IgA nephropathy

Jing Wang, Robert A. Anders, Qiang Wu, Dacheng Peng, Judy H. Cho, Yonglian Sun, Reda Karaliukas, Hyung Sik Kang, Jerrold R. Turner, Yang Xin Fu

Research output: Contribution to journalArticle

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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 β receptor (LTβR), 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 LTβR 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.

Original languageEnglish (US)
Pages (from-to)826-835
Number of pages10
JournalJournal of Clinical Investigation
Volume113
Issue number6
DOIs
StatePublished - Mar 1 2004

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IGA Glomerulonephritis
Immunoglobulin A
Inflammation
T-Lymphocytes
Light
Lymphotoxin-alpha
Hematuria
Serum
Inflammatory Bowel Diseases
Ligands

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Dysregulated LIGHT expression on T cells mediates intestinal inflammation and contributes to IgA nephropathy. / Wang, Jing; Anders, Robert A.; Wu, Qiang; Peng, Dacheng; Cho, Judy H.; Sun, Yonglian; Karaliukas, Reda; Kang, Hyung Sik; Turner, Jerrold R.; Fu, Yang Xin.

In: Journal of Clinical Investigation, Vol. 113, No. 6, 01.03.2004, p. 826-835.

Research output: Contribution to journalArticle

Wang, J, Anders, RA, Wu, Q, Peng, D, Cho, JH, Sun, Y, Karaliukas, R, Kang, HS, Turner, JR & Fu, YX 2004, 'Dysregulated LIGHT expression on T cells mediates intestinal inflammation and contributes to IgA nephropathy', Journal of Clinical Investigation, vol. 113, no. 6, pp. 826-835. https://doi.org/10.1172/JCI200420096
Wang, Jing ; Anders, Robert A. ; Wu, Qiang ; Peng, Dacheng ; Cho, Judy H. ; Sun, Yonglian ; Karaliukas, Reda ; Kang, Hyung Sik ; Turner, Jerrold R. ; Fu, Yang Xin. / Dysregulated LIGHT expression on T cells mediates intestinal inflammation and contributes to IgA nephropathy. In: Journal of Clinical Investigation. 2004 ; Vol. 113, No. 6. pp. 826-835.
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