Background Oligodeoxynucleotides (ODNs) containing unmethylated cytosine–guanosine (CpG) sequence motifs constitute the immunostimulatory components of bacterial DNA which potently activate innate immunity. Administration of CpG-ODNs before the onset of experimental colitis prevents intestinal inflammation by induction of colitis-suppressing T cells.
Aims To identify the interplay between innate and adaptive immune cells finally leading to protective CpG-ODN effects in intestinal inflammation.
Methods Total splenic cells or purified selected cell types (CD4+CD62L+ T cells alone or with B cells or dendritic cells (DCs)) from BALB/c mice were (co)-incubated in vitro with CpG-ODN for 5 days and CD4+CD62L+ cells were injected intraperitoneally into C.B.-17 SCID (severe combined immunodeficiency) mice. Splenic CD4+CD62L+ T cells were isolated from transgenic donor mice in which CD11c+ DCs were depleted by diphtheria toxin administration during CpG-ODN treatment and injected into C57BL/6 Rag2−/− recipients. Intestinal inflammation was evaluated by histological scoring and cytokine secretion of mesenteric lymph node cells.
Results CpG-ODN treatment of total splenic cells but not of purified CD4+CD62L+ cells reduced the colitogenic potential of transferred T cells. While CpG-ODN stimulation of co-cultured CD4+CD62L+ and B-cells did not alter the colitogenic potential of T cells, co-incubation of CpG-ODN-stimulated DCs and CD4+CD62L+ cells reduced the colitogenic potential of the T cell population. Depletion of CD11c+ DCs during CpG-ODN administration in vivo abolished the protective CpG-ODN effects.
Conclusions CpG-ODN-dependent protective effects in experimental colitis act indirectly on CD4+CD62L+ T cells. While the involvement of B cells could be excluded, CD11c+ DCs were identified as key mediators of CpG-ODN-induced protection in experimental colitis.
- Dendritic cells
- experimental colitis
- IBD basic research
- mucosal immunology
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Funding This work was supported by a DFG grant to FO (OB 135/10-2).
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.