Aberrant activation of nuclear factor of activated T cell 2 in lamina propria mononuclear cells in ulcerative colitis

Tsung Chieh Shih, Sen Yung Hsieh*, Yi Yueh Hsieh, Tse Chin Chen, Chien Yu Yeh, Chun Jung Lin, Deng Yn Lin, Cheng Tang Chiu

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

17 Scopus citations

Abstract

Aim: To investigate the role of nuclear factor of activated T cell 2 (NFAT2), the major NFAT protein in peripheral T cells, in sustained T cell activation and intractable inflammation in human ulcerative colitis (UC). Methods: We used two-dimensional gel-electrophoresis, immunohistochemistry, double immunohistochemical staining, and confocal microscopy to inspect the expression of NFAT2 in 107, 15, 48 and 5 cases of UC, Crohn's disease (CD), non-specific colitis, and 5 healthy individuals, respectively. Results: Up-regulation with profound nucleo-translocation/activation of NFAT2 of lamina propria mononuclear cells (LPMC) of colonic mucosa was found specifically in the affected colonic mucosa from patients with UC, as compared to CD or NC (P < 0.001, Kruskal-Wallis test). Nucleo-translocation/activation of NFAT2 primarily occurred in CD8+T, but was less prominent in CD4+ T cells or CD20+B cells. It was strongly associated with the disease activity, including endoscopic stage (τ = 0.2145, P = 0.0281) and histologic grade (τ = 0.4167, P < 0.001). Conclusion: We disclose for the first time the nucleo-translocation/ activatin of NFAT2 in lamina propria mononuclear cells in ulcerative colitis. Activation of NFAT2 was specific for ulcerative colitis and highly associated with disease activity. Since activation of NFAT2 is implicated in an auto-regulatory positive feedback loop of sustained T-cell activation and NFAT proteins play key roles in the calcium/ calcineurin signaling pathways, our results not only provide new insights into the mechanism for sustained intractable inflammation, but also suggest the calcium-calcineurin/NFAT pathway as a new therapeutic target for ulcerative colitis.

Original languageEnglish
Pages (from-to)1759-1767
Number of pages9
JournalWorld Journal of Gastroenterology
Volume14
Issue number11
DOIs
StatePublished - 21 03 2008
Externally publishedYes

Keywords

  • Inflammatory bowel disease
  • Nuclear factor of activated T cells
  • Nuclear factor of activated T cells 2
  • Nuclear factor of activated T cells c1
  • Ulcerative colitis

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