Hofmann, Claudia and Dunger, Nadja and Doser, Kristina and Lippert, Elisabeth and Siller, Sebastian and Edinger, Matthias and Falk, Werner and Obermeier, Florian (2014) Physiologic TLR9-CpG-DNA Interaction Is Essential for the Homeostasis of the Intestinal Immune System. INFLAMMATORY BOWEL DISEASES, 20 (1). pp. 136-143. ISSN 1078-0998, 1536-4844
Full text not available from this repository. (Request a copy)Abstract
Background:Cytosine-guanosine dinucleotide (CpG) motifs are immunostimulatory components of bacterial DNA and activators of innate immunity through Toll-like receptor 9 (TLR9). Administration of CpG oligodeoxynucleotides before the onset of experimental colitis prevents intestinal inflammation by enforcement of regulatory mechanisms. It was investigated whether physiologic CpG/TLR9 interactions are critical for the homeostasis of the intestinal immune system.Methods:Mesenteric lymph node cell and lamina propria mononuclear cell (LPMC) populations from BALB/c wild-type (wt) or TLR9(-/-) mice were assessed by flow cytometry and proteome profiling. Cytokine secretion was determined and nuclear extracts were analyzed for nuclear factor kappa B (NF-B) and cAMP response-element binding protein activity. To assess the colitogenic potential of intestinal T cells, CD4(+)-enriched cells from LPMC of wt or TLR9(-/-) donor mice were injected intraperitoneally in recipient CB-17 SCID mice.Results:TLR9 deficiency was accompanied by slight changes in cellular composition and phosphorylation of signaling proteins of mesenteric lymph node cell and LPMC. LPMC from TLR9(-/-) mice displayed an increased proinflammatory phenotype compared with wt LPMC. NF-B activity in cells from TLR9(-/-) mice was enhanced, whereas cAMP response-element binding activity was reduced compared with wt. Transfer of lamina propria CD4(+)-enriched T cells from TLR9(-/-) mice induced severe colitis, whereas wt lamina propria CD4(+)-enriched T cells displayed an attenuated phenotype.Conclusions:Lack of physiologic CpG/TLR9 interaction impairs the function of the intestinal immune system indicated by enhanced proinflammatory properties. Thus, physiologic CpG/TLR interaction is essential for homeostasis of the intestinal immune system as it is required for the induction of counterregulating anti-inflammatory mechanisms.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INFLAMMATORY BOWEL DISEASES; TOLL-LIKE RECEPTOR-9; DENDRITIC CELLS; EXPERIMENTAL COLITIS; BACTERIAL-DNA; CPG MOTIFS; T-CELLS; MICE; REGULATORS; TISSUE; TLR9; intestinal immune system; homeostasis; NF-B; CREB |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Nov 2019 13:49 |
| Last Modified: | 29 Nov 2019 13:49 |
| URI: | https://pred.uni-regensburg.de/id/eprint/11092 |
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