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Logo of bmcgastBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Gastroenterology
BMC Gastroenterol. 2012; 12: 97.
Published online Jul 31, 2012. doi:  10.1186/1471-230X-12-97
PMCID: PMC3449180
Deletion of Foxp3+ regulatory T cells in genetically targeted mice supports development of intestinal inflammation
Franziska Boehm,1 Maria Martin,1 Rebecca Kesselring,1 Gabriela Schiechl,1 Edward K Geissler,1 Hans-Jürgen Schlitt,1 and Stefan Fichtner-Feiglcorresponding author1
1Department of Surgery, University of Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg, 93053, Germany
corresponding authorCorresponding author.
Franziska Boehm: franziska-boehm/at/; Maria Martin: maria.martin/at/; Rebecca Kesselring: rebecca.kesselring/at/; Gabriela Schiechl: gabriela.schiechl/at/; Edward K Geissler: edward.geissler/at/; Hans-Jürgen Schlitt: hans.schlitt/at/; Stefan Fichtner-Feigl: stefan.fichtner/at/
Received September 3, 2010; Accepted July 11, 2012.
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.
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.
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.
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.
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