Tumor necrosis factor-receptor 2 is up-regulated on lamina propria T cells in Crohn's disease and promotes experimental colitis in vivo

Eur J Immunol. 2002 Nov;32(11):3142-51. doi: 10.1002/1521-4141(200211)32:11<3142::AID-IMMU3142>3.0.CO;2-4.


Tumor necrosis factor (TNF) plays a pivotal role in the pathogenesis of Crohn's disease (CD). However, little is known about the role of TNF receptors (TNF-R) in this disease. Here, we found that TNF-R2 (in contrast to TNF-R1) was significantly up-regulated on lamina propria and peripheral blood T cells in CD compared to control patients. To directly test the functional role of TNF-R2 in Th1-mediated experimental colitis in vivo, we took advantage of transgenic animals overexpressing TNF-R2 in T cells. Reconstitution of SCID mice with CD4+ CD62L+ T cells from TNF-R2 transgenic mice led to an earlier wasting syndrome, a more severe colitis and augmented Th1 cytokine production than reconstitution with cells from wild-type littermates. In addition, TUNEL staining revealed a significantly decreased apoptosis rate of lamina propria mononuclear cells in mice reconstituted with TNF-R2 transgenic T cells compared to mice reconstituted with wild-type T cells. In summary, our data suggest a critical regulatory role of TNF-R2 signaling for disease exacerbation in Th1-mediated chronic colitis. Taken together with the increased expression of TNF-R2 in CD, selective targeting of TNF-R2 signaling thus emerges as a potentially novel approach to the treatment of CD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antigens, CD / biosynthesis
  • Antigens, CD / physiology*
  • Apoptosis
  • Chronic Disease
  • Colitis / immunology*
  • Colon / immunology*
  • Crohn Disease / etiology
  • Crohn Disease / immunology*
  • Female
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-4 / biosynthesis
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, SCID
  • Mice, Transgenic
  • Middle Aged
  • Receptors, Tumor Necrosis Factor / biosynthesis
  • Receptors, Tumor Necrosis Factor / physiology*
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • T-Lymphocytes / metabolism*
  • Up-Regulation


  • Antigens, CD
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Interleukin-4
  • Interferon-gamma