1. Intestinal Lamina Propria Dendritic Cell Subsets Have Different Origin and Functions
- Author
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Wolf-Dietrich Hardt, Chen Varol, Guy Shakhar, Steffen Jung, Hans Joerg Fehling, Alexandra Vallon-Eberhard, Hervé Luche, Eran Elinav, Yami Shapira, and Tegest Aychek
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CD14 ,Cellular differentiation ,Immunology ,Biology ,Receptors, Interleukin-8A ,Mice ,Immune system ,Antigens, CD ,Cell Line, Tumor ,medicine ,Immunology and Allergy ,Animals ,Homeostasis ,Cell Lineage ,Intestinal Mucosa ,MOLIMMUNO ,Lamina propria ,CD11b Antigen ,Granulocyte-Macrophage Colony-Stimulating Factor ,Cell Differentiation ,Dendritic cell ,Dendritic Cells ,Colitis ,Cell biology ,Mice, Inbred C57BL ,Disease Models, Animal ,Lymphatic system ,medicine.anatomical_structure ,Infectious Diseases ,Phenotype ,Integrin alpha M ,fms-Like Tyrosine Kinase 3 ,Cell culture ,CELLIMMUNO ,biology.protein ,Integrin alpha Chains - 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(+) CX(3)CR1(-) lpDCs arose from macrophage-DC precursors (MDPs) via DC-committed intermediates (pre-cDCs) through a Flt3L growth-factor-mediated pathway. CD11b(+) CD14(+) CX(3)CR1(+) lpDCs were derived from grafted Ly6C(hi) but not Ly6C(lo) monocytes under the control of GM-CSF. Mice reconstituted exclusively with CX(3)CR1(+) lpDCs when challenged in an innate colitis model developed severe intestinal inflammation that was driven by graft-derived TNF-alpha-secreting CX(3)CR1(+) lpDCs. Our results highlight the critical importance of the lpDC subset balance for robust gut homeostasis.
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