Boehm, Franziska and Martin, Maria and Kesselring, Rebecca and Schiechl, Gabriela and Geissler, Edward K. and Schlitt, Hans-Juergen and Fichtner-Feigl, Stefan (2012) Deletion of Foxp3(+) regulatory T cells in genetically targeted mice supports development of intestinal inflammation. BMC GASTROENTEROLOGY, 12: 97. ISSN 1471-230X,
Full text not available from this repository. (Request a copy)Abstract
Background: 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-gamma, 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANSCRIPTION FACTOR FOXP3; ULCERATIVE-COLITIS; BOWEL-DISEASE; DEPENDENT COLITIS; CROHNS-DISEASE; HOMEOSTASIS; MUCOSAL; MAINTENANCE; SCURFIN; INNATE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 May 2020 05:32 |
| Last Modified: | 11 May 2020 05:32 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18422 |
Actions (login required)
 |
View Item |
