The Transcription Factor NFATc2 Controls Apoptosis and Activation of T Cells by IL-6 in Colitis

Details

Serval ID
serval:BIB_90492F32296E
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Institution
Title
The Transcription Factor NFATc2 Controls Apoptosis and Activation of T Cells by IL-6 in Colitis
Title of the conference
10th Annual Meeting of the Federation of Clinical Immunology Societies
Author(s)
Weigmann Benno, Lehr Hans-Anton, Rose-John Stefan, Neurath Markus
Address
Boston (MA) - United States, 24-27 June 2010
ISBN
1540-9538[electronic], 0022-1007[linking]
Publication state
Published
Issued date
2010
Volume
135
Series
Clinical Immunology
Pages
S65-S66
Language
english
Notes
Meeting Abstract
Abstract
The nuclear factor of activated T cells (NFAT) family of transcription factors controls calcium signaling in T lymphocytes. In this study, we have identified a crucial regulatory role of the transcription factor NFATc2 in T cell-dependent experimental colitis. Similar to ulcerative colitis in humans, the expression of NFATc2 was up-regulated in oxazolone-induced chronic intestinal inflammation. Furthermore, NFATc2 deficiency suppressed colitis induced by oxazolone administration. This finding was associated with enhanced T cell apoptosis in the lamina propria and strikingly reduced production of IL-6, -13, and -17 by mucosal T lymphocytes. Further studies using knockout mice showed that IL-6, rather than IL-23 and -17, are essential for oxazolone colitis induction. Administration of hyper-IL-6 blocked the protective effects of NFATc2 deficiency in experimental colitis, suggesting that IL-6 signal transduction plays a major pathogenic role in vivo. Finally, adoptive transfer of IL-6 and wild-type T cells demonstrated that oxazolone colitis is critically dependent on IL-6 production by T cells. Collectively, these results define a unique regulatory role for NFATc2 in colitis by controlling mucosal T cell activation in an IL-6-dependent manner. NFATc2 in T cells thus emerges as a potentially new therapeutic target for inflammatory bowel diseases.
Web of science
Create date
02/09/2010 11:43
Last modification date
20/08/2019 14:53
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