The critical role of LIGHT in promoting intestinal inflammation and Crohn's disease

Jing Wang, Robert A. Anders, Yang Wang, Jerrold R. Turner, Clara Abraham, Klaus Pfeffer, Yang Xin Fu

Research output: Contribution to journalArticle

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Abstract

Crohn's disease (CD) is a type of inflammatory bowel disease associated with increased Th1 cytokines and unique pathological features. However, its pathogenesis has not been fully understood. Previous studies showed that homologous to lymphotoxin, exhibits inducible expression, competes with herpesvirus glycoprotein D for HVEM on T cells (LIGHT) transgenic (Tg) mice develop autoimmunity including intestinal inflammation with a variable time course. In this study, we establish an experimental model for CD by adoptive transfer of Tg mesenteric lymph node cells into RAG-/- mice. The recipients of Tg lymphocytes rapidly develop a disease strikingly similar to the key pathologic features and cytokine characterization observed in CD. We demonstrate that, as a costimulatory molecule, LIGHT preferentially drives Th1 responses. LIGHT-mediated intestinal disease is dependent on both of its identified signaling receptors, lymphotoxin β receptor and herpes virus entry mediator, because LIGHT Tg mesenteric lymph node cells do not cause intestinal inflammation when transferred into the lymphotoxin β receptor-deficient mice, and herpes virus entry mediator on donor T cells is required for the full development of disease. Furthermore, we demonstrated that up-regulation of LIGHT is associated with active CD. These data establish a new mouse model resembling CD and suggest that up-regulation of LIGHT may be an important mediator of CD pathogenesis.

Original languageEnglish (US)
Pages (from-to)8173-8182
Number of pages10
JournalJournal of Immunology
Volume174
Issue number12
StatePublished - Jun 15 2005

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Intestinal Diseases
Crohn Disease
Inflammation
Light
Lymphotoxin-alpha
Virus Internalization
Up-Regulation
Lymph Nodes
Cytokines
T-Lymphocytes
Adoptive Transfer
Herpesviridae
Autoimmunity
Inflammatory Bowel Diseases
Transgenic Mice
Glycoproteins
Theoretical Models
Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Wang, J., Anders, R. A., Wang, Y., Turner, J. R., Abraham, C., Pfeffer, K., & Fu, Y. X. (2005). The critical role of LIGHT in promoting intestinal inflammation and Crohn's disease. Journal of Immunology, 174(12), 8173-8182.

The critical role of LIGHT in promoting intestinal inflammation and Crohn's disease. / Wang, Jing; Anders, Robert A.; Wang, Yang; Turner, Jerrold R.; Abraham, Clara; Pfeffer, Klaus; Fu, Yang Xin.

In: Journal of Immunology, Vol. 174, No. 12, 15.06.2005, p. 8173-8182.

Research output: Contribution to journalArticle

Wang, J, Anders, RA, Wang, Y, Turner, JR, Abraham, C, Pfeffer, K & Fu, YX 2005, 'The critical role of LIGHT in promoting intestinal inflammation and Crohn's disease', Journal of Immunology, vol. 174, no. 12, pp. 8173-8182.
Wang J, Anders RA, Wang Y, Turner JR, Abraham C, Pfeffer K et al. The critical role of LIGHT in promoting intestinal inflammation and Crohn's disease. Journal of Immunology. 2005 Jun 15;174(12):8173-8182.
Wang, Jing ; Anders, Robert A. ; Wang, Yang ; Turner, Jerrold R. ; Abraham, Clara ; Pfeffer, Klaus ; Fu, Yang Xin. / The critical role of LIGHT in promoting intestinal inflammation and Crohn's disease. In: Journal of Immunology. 2005 ; Vol. 174, No. 12. pp. 8173-8182.
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