Bleich, Andre and Janus, Lydia M. and Smoczek, Anna and Westendorf, Astrid M. and Strauch, Ulrike and Maehler, Michael and Hedrich, Hans-J. and Fichtner-Feigl, Stefan and Schoelmerich, Juergen and Falk, Werner and Hofmann, Claudia and Obermeier, Florian (2009) CpG Motifs of Bacterial DNA Exert Protective Effects in Mouse Models of IBD by Antigen-Independent Tolerance Induction. GASTROENTEROLOGY, 136 (1). pp. 278-287. ISSN 0016-5085,
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Background & Aims: Prophylactic treatment of mice with CpG motifs of bacterial DNA protects from experimental inflammatory bowel disease, at least partly via induction of inhibitory T-cells. The aim of this study was to elucidate whether these CpG-dependent protective effects require presence of bacterial flora suggesting antigen-specific regulatory activity. Methods: Germ-free BALB/c and IL-10(-/-) mice were treated with CpG-oligodeoxynucleotides (ODN), control-ODN, or PBS. CD4(+)CD62L(+) cells of these mice were transferred into SCID recipients. CpG-ODN-treated germ-free IL-10(-/-) mice were transferred into colitogenic environment. Monoclonal antibodies were used to neutralize TGF-beta and IFN-alpha/beta during CpG-ODN treatment. CD4(+)CD62L(+) cells of donors were evaluated for cytokine secretion and FOXP3, PD-1, and CD25 expression. Results: Compared to PBS or control-ODN treatment, CpG-ODN application to germ-free donors led to decreased intestinal inflammation as indicated by histology, decreased proinflammatory cytokines, and increased IL-10 secretion. Protection was also observed after cotransfer of cells from PBS and CpG-ODN treated donors. Anti-TGF-beta and anti-INF-alpha/beta partly reversed the protective CpG-ODN effect. CpG-ODN-treated germ-free IL-10(-/-) mice transferred into colitogenic environment developed significantly less colitis than controls but not recipients of IL-10(-/-) CD4(+)CD62L(+) cells. CD4(+)CD62L(+) cells of CpG-treated germ-free animals displayed increased expression of regulatory markers. Conclusions: Even without pre-existence of bacterial flora CpG-ODN exposition induces tolerance, indicating that CpG-ODN-induced regulatory T-cells are not bacterial antigen specific. TGF-beta and IFN-alpha/beta play major roles in induction of regulatory cells, and although IL10-independent mechanisms play a role in CpG-ODN protection, this cytokine likely is important for the effector mechanism of CpG-ODN-induced regulatory T-cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | REGULATORY T-CELLS; INFLAMMATORY-BOWEL-DISEASE; EXPERIMENTAL COLITIS; TGF-BETA; DENDRITIC CELLS; MICE; NOD2; OLIGODEOXYNUCLEOTIDES; OLIGONUCLEOTIDES; DIFFERENTIATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Oct 2020 08:55 |
| Last Modified: | 12 Oct 2020 08:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29729 |
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