In:
BMC Gastroenterology, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2012-12)
Abstract:
Mice lacking Foxp3 + regulatory T (Treg) cells develop severe tissue inflammation in lung, skin, and liver with premature death, whereas the intestine remains uninflamed. This study aims to demonstrate the importance of Foxp3 + Treg for the activation of T cells and the development of intestinal inflammation. Methods Foxp3-GFP-DTR (human diphtheria toxin receptor) C57BL/6 mice allow elimination of Foxp3 + Treg by treatment with Dx (diphtheria toxin). The influence of Foxp3 + Treg on intestinal inflammation was tested using the CD4 + T-cell transfer colitis model in Rag −/− C57BL/6 mice and the acute DSS-colitis model. Results Continuous depletion of Foxp3 + Treg in Foxp3-GFP-DTR mice led to dramatic weight loss and death of mice by day 28. After 10 days of depletion of Foxp3 + Treg, isolated CD4 + T-cells were activated and produced extensive amounts of IFN-γ, IL-13, and IL-17A. Transfer of total CD4 + T-cells isolated from Foxp3-GFP-DTR mice did not result in any changes of intestinal homeostasis in Rag −/− C57BL/6 mice. However, administration of DTx between days 14 and 18 after T-cell reconstitution, lead to elimination of Foxp3 + Treg and to immediate weight loss due to intestinal inflammation. This pro-inflammatory effect of Foxp3 + Treg depletion consecutively increased inflammatory cytokine production. Further, the depletion of Foxp3 + Treg from Foxp3-GFP-DTR mice increased the severity of acute dSS-colitis accompanied by 80% lethality of Treg-depleted mice. CD4 + effector T-cells from Foxp3 + Treg-depleted mice produced significantly more pro-inflammatory cytokines. Conclusion Intermittent depletion of Foxp3 + Treg aggravates intestinal inflammatory responses demonstrating the importance of Foxp3 + Treg for the balance at the mucosal surface of the intestine.
Type of Medium:
Online Resource
ISSN:
1471-230X
DOI:
10.1186/1471-230X-12-97
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2012
detail.hit.zdb_id:
2041351-8
Permalink