Intestinal Lamina Propria Dendritic Cell Subsets Have Different Origin and Functions

Chen Varol, Alexandra Vallon-Eberhard, Eran Elinav, Tegest Aychek, Yami Shapira, Hervé Luche, Hans Jörg Fehling, Wolf Dietrich Hardt, Guy Shakhar, Steffen Jung

Research output: Contribution to journalArticlepeer-review

Abstract

The intestinal immune system discriminates between tolerance toward the commensal microflora and robust responses to pathogens. Maintenance of this critical balance is attributed to mucosal dendritic cells (DCs) residing in organized lymphoid tissue and dispersed in the subepithelial lamina propria. In situ parameters of lamina propria DCs (lpDCs) remain poorly understood. Here, we combined conditional cell ablation and precursor-mediated in vivo reconstitution to establish that lpDC subsets have distinct origins and functions. CD103+ CX3CR1- lpDCs arose from macrophage-DC precursors (MDPs) via DC-committed intermediates (pre-cDCs) through a Flt3L growth-factor-mediated pathway. CD11b+ CD14+ CX3CR1+ lpDCs were derived from grafted Ly6Chi but not Ly6Clo monocytes under the control of GM-CSF. Mice reconstituted exclusively with CX3CR1+ lpDCs when challenged in an innate colitis model developed severe intestinal inflammation that was driven by graft-derived TNF-α-secreting CX3CR1+ lpDCs. Our results highlight the critical importance of the lpDC subset balance for robust gut homeostasis.

Original languageEnglish
Pages (from-to)502-512
Number of pages11
JournalImmunity
Volume31
Issue number3
DOIs
StatePublished - 18 Sep 2009
Externally publishedYes

Keywords

  • CELLIMMUNO
  • MOLIMMUNO

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