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Lymph Node Stromal Cells Support Dendritic Cell-Induced Gut-Homing of T Cells |
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Notes for this articleTo elucidate the role of the LN microenvironment in providing signals for T cell tropism, either gut or skin draining LNs were transplanted into a peripheral site, the popliteal fossa.
MLNs stroma expresses RALDH2 (and also RALDH1 and RALDH3) but culturing MLN stroma + BM-DCs did not upregulate RALDH2 expression in the DCs (BM cells were differentiated into DCs with GM-CSF).
MLNs stroma expresses higher levels of RALDH1,2 and 3 than stroma from pLNs
References 32-34 show intimate interaction between LN stromal cells and DCs
Within the MLNs, CD103+ DCs are able to induce the expression of both alpha4beta7 and CCR9, while CD103- DCs are only capable of inducing alpha4beta7 (35, 36). Because also alpha4beta7+ CCR9- cells were shown to migrate to the intestines, both DC subsets can induce gut-homing tropism (9).
CD103+ DCs migrate from the LP to the MLNs CD103- DCs enter MLNs via blood refs 1 35-38
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AbstractT cells are imprinted to express tissue-specific homing receptors upon activation in tissue-draining lymph nodes, resulting in their migration to the site of Ag entry. Expression of gut-homing molecules alpha4beta7 and CCR9 is induced by retinoic acid, a vitamin A metabolite produced by retinal dehydrogenases, which are specifically expressed in dendritic cells as well as stromal cells in mucosa-draining lymph nodes. In this study, we demonstrate that mesenteric lymph node stromal cell-derived retinoic acid can directly induce the expression of gut-homing molecules on proliferating T cells, a process strongly enhanced by bone marrow-derived dendritic cells in vitro. Therefore, cooperation of sessile lymph node stromal cells with mobile dendritic cells warrants the imprinting of tissue specific homing receptors on activated T cells. 10.4049/jimmunol.0900311
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