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

Författare

Summary, in English

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.

Publiceringsår

2015

Språk

Engelska

Sidor

2888-2899

Publikation/Tidskrift/Serie

Journal of Immunology

Volym

195

Issue

6

Dokumenttyp

Artikel i tidskrift

Förlag

American Association of Immunologists

Ämne

  • Immunology in the medical area

Status

Published

Forskningsgrupp

  • Adaptive Immunity
  • Immunology
  • Mucosal Immunology

ISBN/ISSN/Övrigt

  • ISSN: 1550-6606