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In This Issue, The Journal of Immunology, Volume 176, Issue 9, May 2006, Pages 5131–5132, https://doi.org/10.4049/jimmunol.176.9.5131
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Extract
Intestinal DC Migration and Activation
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Factors controlling peripheral activation of intestinal lymph dendritic cells (iL-DCs) and their migration to mesenteric lymph nodes (MLNs) are difficult to evaluate in vivo. Yrlid et al. (p. 5205 ) detected a dramatic increase in iL-DCs in lymph from thoracic duct-cannulated rats orally fed a TLR7/8 ligand, R-848, 2 h earlier compared with controls. The iL-DCs had up-regulated CD25, but not CD86, expression. There also was a dramatic increase in DCs in T cell areas and interfollicular regions of intestine and MLNs and in interfollicular T cell areas of Peyer’s patches as determined by immunofluorescence; DCs were lost from the lamina propria and subepithelial domes of Peyer’s patches. In contrast, DCs purified from MLNs 18 h after receiving R-848 had greater CD25 and CD86 expression than MLN-DCs from control rats. Mice, whose iL-DCs had a similar response to R-848, had high serum levels of IL-6, IL-12p70, TNF-α, and IFN-α; plasmacytoid DCs (pDCs) purified from MLNs were the source of the cytokines. Anti-TNF-α mAb treatment of mice abrogated DC accumulation in MLNs in response to oral R-848; CD86 expression was up-regulated on their MLN-DCs and pDCs. MLN-DCs and pDCs of mice deficient in IFN-αβ had minimal increase in CD86 expression after R-848 administration. Serum levels of IL-12p70, TNF-α and IFN-α, MLN-DCs numbers, and CD86 expression were reduced in R-848-fed mice previously given a pDC-depleting Ab. The authors use rat and mouse models to demonstrate TNF-α-dependent MLN accumulation of iL-DCs and their IFN-α-dependent peripheral activation in response to TLR7/8 stimulation.
