Heterogeneity of dendritic cells in the mouse liver: identification and characterization of four distinct populations.
Liver dendritic cells (DC) are believed to play important roles in liver immunity, autoimmunity, and in the regulation of hepatic allograft acceptance. However, limited information is available on the phenotypes and functions of DC in the liver. To address this issue, we isolated DC from murine liver using procedures that do not involve collagenase, and characterized the freshly isolated DC population that had not been subjected to in vitro expansion. Thence, based on the expression of CD4, B220, and CD11b, four subsets or groups of hepatic NK1.1(-)CD11c(+) DC were identified with the following phenotypes: B220(+)CD4(+), B220(+)CD4(-), B220(-)CD11b(+), and B220(-)CD11b(-). Each subset was further characterized both phenotypically and functionally. In addition to unique phenotypic expression, each subset displayed different allostimulation capability in mixed lymphocyte reaction assays. All four groups developed DC morphology following in vitro culture with activation agents and synthesized distinct patterns of cytokines in response to different stimuli. Taken together, our results suggest that groups I and II are IFN-alpha-producing plasmacytoid DC, group III cells are myeloid-related DC, while group IV is a heterogeneous population containing both myeloid- and lymphoid-related DC. Our results demonstrate the highly heterogeneous nature of hepatic DC, which is in agreement with the unique requirements for APC in the complex liver environment.
Lian
Zhe-Xiong
ZX
Division of Rheumatology/Allergy/Clinical Immunology, University of California, Davis, CA 95616, USA.
Okada
Tomoyuki
T
He
Xiao-Song
XS
Kita
Hiroto
H
Liu
Yong-Jun
YJ
Ansari
Aftab A
AA
Kikuchi
Kentaro
K
Ikehara
Susumu
S
Gershwin
M Eric
ME
D000818:Animals; D000941:Antigens / Q000096:biosynthesis; D000950:Antigens, Ly; D000954:Antigens, Surface / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D039481:CD11b Antigen / Q000096:biosynthesis; D039521:CD11c Antigen / Q000096:biosynthesis; D015704:CD4 Antigens / Q000096:biosynthesis; D019070:Cell Lineage / Q000276:immunology; D002469:Cell Separation / Q000379:methods; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D017364:Collagenases / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000145:classification / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D029721:Drosophila Proteins; D016130:Immunophenotyping; D007519:Isoantigens / Q000276:immunology; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008024:Ligands; D008099:Liver / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010477:Perfusion; D014176:Protein Biosynthesis; D011506:Proteins; D011956:Receptors, Cell Surface / Q000378:metabolism; D051193:Toll-Like Receptors
D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D015415:Biomarkers; D039481:CD11b Antigen; D039521:CD11c Antigen; D015704:CD4 Antigens; D016207:Cytokines; D029721:Drosophila Proteins; D007519:Isoantigens; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D008024:Ligands; D008562:Membrane Glycoproteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D017493:Leukocyte Common Antigens; D017364:Collagenases