T cell-dependent protective effects of CpG motifs of bacterial DNA in experimental colitis are mediated by CD11c+ dendritic cells. Issue 10 (23rd August 2010)

• Record Type: Journal Article
• Authors: Hofmann, Claudia; Dunger, Nadja; Grunwald, Nicole; Hämmerling, Günter J; Hoffmann, Petra; Schölmerich, Jürgen; Falk, Werner; Obermeier, Florian
• Is Part Of: Gut. Volume 59:Issue 10(2010)
• Page Start: 1347
• Page End: 1354
• Publication Date: 2010-08-23
• Subjects: Dendritic cells -- experimental colitis -- TLR9 -- CpG -- IBD basic research -- mucosal immunology; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gut.2009.193177
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : 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.