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. 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.
Varol
Chen
C
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel 76100.
Vallon-Eberhard
Alexandra
A
Elinav
Eran
E
Aychek
Tegest
T
Shapira
Yami
Y
Luche
Hervé
H
Fehling
Hans Jörg
HJ
Hardt
Wolf-Dietrich
WD
Shakhar
Guy
G
Jung
Steffen
S
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D039481:CD11b Antigen / Q000276:immunology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D019070:Cell Lineage; D003092:Colitis / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006706:Homeostasis; D039001:Integrin alpha Chains / Q000276:immunology; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D023062:Receptors, Interleukin-8A / Q000276:immunology; D051941:fms-Like Tyrosine Kinase 3 / Q000276:immunology
D015703:Antigens, CD; D039481:CD11b Antigen; D039001:Integrin alpha Chains; D023062:Receptors, Interleukin-8A; C091367:alpha E integrins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3