MyD88 Signaling Regulates Steady-State Migration of Intestinal CD103+ Dendritic Cells Independently of TNF-α and the Gut Microbiota

Karin Hägerbrand, Jessica Westlund, Ulf Yrlid, William Winston Agace, Bengt Johansson Lindbom

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    Intestinal homeostasis and induction of systemic tolerance to fed Ags (i.e., oral tolerance) rely on the steady-state migration of smallintestinal lamina propria dendritic cells (DCs) into draining mesenteric lymph nodes (MLN). The majority of these migratory DCs express the α integrin chain CD103, and in this study we demonstrate that the steady-state mobilization of CD103+ DCs into the MLN is in part governed by the IL-1R family/TLR signaling adaptor molecule MyD88. Similar to mice with complete MyD88 deficiency, specific deletion of MyD88 in DCs resulted in a 50–60% reduction in short-term accumulation of both CD103+CD11b+and CD103+CD11b- DCs in the MLN. DC migration was independent of caspase-1, which is responsible for the inflammasomedependentproteolytic activation of IL-1 cytokine family members, and was not affected by treatment with broad-spectrumantibiotics. Consistent with the latter finding, the proportion and phenotypic composition of DCs were similar in mesentericlymph from germ-free and conventionally housed mice. Although TNF-α was required for CD103+ DC migration to the MLN after oral administration of the TLR7 agonist R848, it was not required for the steady-state migration of these cells. Similarly,TLR signaling through the adaptor molecule Toll/IL-1R domain-containing adapter inducing IFN-b and downstream productionof type I IFN were not required for steady-state CD103+ DC migration. Taken together, our results demonstrate that MyD88 signaling in DCs, independently of the microbiota and TNF-a, is required for optimal steady-state migration of small intestinallamina propria CD103+ DCs into the MLN.
    Original languageEnglish
    JournalJournal of Immunology
    Volume195
    Issue number6
    Pages (from-to)2888-2899
    Number of pages12
    ISSN0022-1767
    DOIs
    Publication statusPublished - 2015

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