title: Complement receptor C5aR1/CD88 and dipeptidyl peptidase-4/CD26 define distinct hematopoietic lineages of dendritic cells.
abstract: Differential display of the integrins CD103 and CD11b are widely used to distinguish two major dendritic cell (DC) subsets in nonlymphoid tissues. CD103(+) DCs arise from FLT3-dependent DC precursors (preDCs), whereas CD11b(hi) DCs can arise either from preDCs or FLT3-independent monocytes. Functional characterization of these two lineages of CD11b(hi) DCs has been hindered by the lack of a widely applicable method to distinguish between them. We performed gene expression analysis of fractionated lung DCs from C57BL/6 mice and found that monocyte-derived DCs (moDCs), including CD11b(hi)Ly-6C(lo) tissue-resident and CD11b(hi)Ly-6C(hi) inflammatory moDCs, express the complement 5a receptor 1/CD88, whereas preDC-derived conventional DCs (cDCs), including CD103(+) and CD11b(hi) cDCs, express dipeptidyl peptidase-4/CD26. Flow cytometric analysis of multiple organs, including the kidney, liver, lung, lymph nodes, small intestine, and spleen, confirmed that reciprocal display of CD88 and CD26 can reliably distinguish FLT3-independent moDCs from FLT3-dependent cDCs in C57BL/6 mice. Similar results were obtained when DCs from BALB/c mice were analyzed. Using this novel approach to study DCs in mediastinal lymph nodes, we observed that most blood-derived lymph node-resident DCs, as well as tissue-derived migratory DCs, are cDCs. Furthermore, cDCs, but not moDCs, stimulated naive T cell proliferation. We anticipate that the use of Abs against CD88 and CD26 to distinguish moDCs and cDCs in multiple organs and mouse strains will facilitate studies aimed at assigning specific functions to distinct DC lineages in immune responses.
authors.affiliation: Immunity, Inflammation and Disease Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709; nakanoh@niehs.nih.gov.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakano
authors.affiliation: Immunity, Inflammation and Disease Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709; Division of Allergy and Immunology, Department of Pediatrics, Duke University Medical Center, Durham, NC 27705;
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Moran
authors.affiliation: Immunity, Inflammation and Disease Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709;
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakano
authors.affiliation: Molecular Genetics Core Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709; and.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Gerrish
authors.affiliation: Signal Transduction Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709.
authors.forename: Carl D
authors.initials: CD
authors.lastname: Bortner
authors.affiliation: Immunity, Inflammation and Disease Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709;
authors.forename: Donald N
authors.initials: DN
authors.lastname: Cook
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D039481:CD11b Antigen / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation / Q000502:physiology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D039001:Integrin alpha Chains / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D044087:Receptor, Anaphylatoxin C5a / Q000235:genetics / Q000276:immunology*; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics / Q000276:immunology
chemical_list: D015703:Antigens, CD; C000591759:C5ar1 protein, mouse; D039481:CD11b Antigen; D039001:Integrin alpha Chains; D044087:Receptor, Anaphylatoxin C5a; C091367:alpha E integrins; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3; D018819:Dipeptidyl Peptidase 4; C545245:Dpp4 protein, mouse