CCR9 expression defines tolerogenic plasmacytoid dendritic cells able to suppress acute graft-versus-host disease.
Dendritic cells (DCs) are 'professional' antigen-presenting cells that are key in the regulation of immune responses. Here we characterize a unique subset of tolerogenic DCs that expressed the chemokine receptor CCR9 and migrated to the CCR9 ligand CCL25, a chemokine linked to the homing of T cells and DCs to the gut. CCR9(+) DCs were of the plasmacytoid DC (pDC) lineage, had an immature phenotype and rapidly downregulated CCR9 in response to maturation-inducing pDC-restricted Toll-like receptor ligands. CCR9(+) pDCs were potent inducers of regulatory T cell function and suppressed antigen-specific immune responses both in vitro and in vivo, including inhibiting acute graft-versus-host disease induced by allogeneic CD4(+) donor T cells in irradiated recipients. Our results identify a highly immunosuppressive population of pDCs present in lymphoid tissues.
Hadeiba
Husein
H
Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA. hadeiba@stanford.edu
Sato
Tohru
T
Habtezion
Aida
A
Oderup
Cecilia
C
Pan
Junliang
J
Butcher
Eugene C
EC
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D019742:Chemokines, CC / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation; D006086:Graft vs Host Disease / Q000276:immunology*; D007422:Intestines / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008024:Ligands; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D054447:Receptors, CCR10 / Q000276:immunology* / Q000378:metabolism; D017634:Self Tolerance; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D051193:Toll-Like Receptors / Q000378:metabolism; D023001:Transplantation Tolerance; D000097628:Chemokine Receptor D6
D015415:Biomarkers; D019742:Chemokines, CC; D017493:Leukocyte Common Antigens; D008024:Ligands; D054447:Receptors, CCR10; D051193:Toll-Like Receptors; D000097628:Chemokine Receptor D6; C491541:Ccl25 protein, mouse; C516770:Ptprc protein, mouse