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Intestinal Lamina Propria Dendritic Cell Subsets Have Different Origin and Functions

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....

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2009-09, Vol.31 (3), p.502-512
Main Authors: Varol, Chen, Vallon-Eberhard, Alexandra, Elinav, Eran, Aychek, Tegest, Shapira, Yami, Luche, Hervé, Fehling, Hans Jörg, Hardt, Wolf-Dietrich, Shakhar, Guy, Jung, Steffen
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Language:English
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Summary: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 + CX 3CR1 − lpDCs arose from macrophage-DC precursors (MDPs) via DC-committed intermediates (pre-cDCs) through a Flt3L growth-factor -mediated pathway. CD11b + CD14 + CX 3CR1 + lpDCs were derived from grafted Ly6C hi but not Ly6C lo monocytes under the control of GM-CSF. Mice reconstituted exclusively with CX 3CR1 + lpDCs when challenged in an innate colitis model developed severe intestinal inflammation that was driven by graft-derived TNF-α-secreting CX 3CR1 + lpDCs. Our results highlight the critical importance of the lpDC subset balance for robust gut homeostasis.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2009.06.025