engleski

Colonic lamina propria dendritic cells in mice with CD4+ T cell-induced colitis

CD11c+ (F4/80– CD68– ) dendritic cells (DC) in the colonic lamina propria (cLP) of normal and immunodeficient (RAG1– /– ) C57BL/6 (B6) mice show high surface expression of MHC class I/ II molecules and CD1d, and low surface expression of CD40, CD80, CD86 costimulator molecules. CD4+ § g T cells from normal or MHC class II-deficient B6 mice transferred into congenic RAG1– /– hosts induce a progressive, lethal colitis. Concomitant with colitis development, DC in the inflamed cLP increase in number and up-regulate surface expression of CD1d, MHC class II molecules and CD40, CD80, CD86 costimulator molecules. cLP DC from non-transplanted (healthy) and transplanted (diseased) mice produce similar amounts of IL-12 p70 and IL-10 in response to CD40 signaling, but the inducible IL-12 p40 release is 5– 15-fold higher in mice with colitis than in non-transplanted mice. Binding of IL-12 p40 to p19 generates IL-23. Freshly isolated cLP lymphocytes (cLPL) from transplanted, diseased mice express 3– 10-fold more p19 transcripts than cLPL from non-transplanted, healthy mice. p19 expression by cLPL is further up-regulated in response to CD40 ligation. Freshly isolated cLP DC from transplanted mice with colitis (but not from non-transplanted controls) stimulate IFN- + (but not IL-4 or IL-13) release by co-cultured NKT cells. In colitis, DC accumulate in the cLP, show an activated surface phenotype, up-regulate IL-12 p40 and p19 expression, and ‘ spontaneously’ stimulate NKT-like cells. cLP DC may be interesting targets for novel therapeutic approaches to modulate mucosal T cell responses in situ.

murine colitis; colonic dendritic cell; mucosal T cell response

nije evidentirano