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Updated: May 15, 2026
08:37
Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
Published on: April 21, 2015
Inhibition of N-terminal ATPase on HSP90 attenuates colitis through enhanced Treg function
C B Collins1, C M Aherne, A Yeckes
1Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.
Mucosal Immunology
|January 17, 2013
Summary
Inhibiting heat-shock protein 90 (HSP90) reduced intestinal inflammation in mouse models of inflammatory bowel disease (IBD). This was linked to increased interleukin-10 (IL-10) production and enhanced regulatory T cell function.
Area of Science:
- Immunology
- Gastroenterology
- Molecular Biology
Background:
- Inflammatory bowel disease (IBD) involves immune dysregulation and increased heat-shock proteins (HSPs).
- HSP90 sequesters heat-shock factor 1 (HSF1), inhibiting anti-inflammatory gene transcription.
Purpose of the Study:
- To investigate if HSP90 inhibition reduces intestinal inflammation in murine IBD models.
- To explore the impact of HSP90 inhibition on regulatory T cells (Tregs) and IL-10 production.
Main Methods:
- Administered 17-allylaminogeldanamycin (17-AAG), an HSP90 inhibitor, to mice with dextran sodium sulfate-induced and CD45RB(High) colitis.
- Assessed colonic inflammation, IL-10 levels, and Treg suppressive capacity in vitro.
- Analyzed HSF1 nuclear localization and target gene expression in Tregs.
Main Results:
- 17-AAG treatment significantly reduced inflammation in both acute and chronic colitis models.
- IL-10 production in the colon was increased following 17-AAG treatment.
- Tregs from 17-AAG treated mice showed enhanced suppressive capacity, dependent on HSF1 and IL-10.
Conclusions:
- HSP90 inhibition demonstrates anti-inflammatory effects in experimental IBD.
- Targeting HSP90 may enhance Treg function and IL-10 production, offering a potential therapeutic strategy for IBD.
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