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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift


Intestinal homeostasis and induction of systemic tolerance to fed Ags (i.e., oral tolerance) rely on the steady-state migration of small intestinal 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 inflammasome-dependent proteolytic activation of IL-1 cytokine family members, and was not affected by treatment with broad-spectrum antibiotics. Consistent with the latter finding, the proportion and phenotypic composition of DCs were similar in mesenteric lymph 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-β and downstream production of 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-α, is required for optimal steady-state migration of small intestinal lamina propria CD103(+) DCs into the MLN.


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Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Immunologi inom det medicinska området
Sidor (från-till)2888-2899
TidskriftJournal of Immunology
StatusPublished - 2015
Peer review utfördJa

Relaterad forskningsoutput

Hägerbrand, K., 2015, Section for Immunology, Lund University. 84 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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