CX3CR1+ CD8alpha+ dendritic cells are a steady-state population related to plasmacytoid dendritic cells.
Lymphoid organs are characterized by a complex network of phenotypically distinct dendritic cells (DC) with potentially unique roles in pathogen recognition and immunostimulation. Classical DC (cDC) include two major subsets distinguished in the mouse by the expression of CD8alpha. Here we describe a subset of CD8alpha(+) DC in lymphoid organs of naïve mice characterized by expression of the CX(3)CR1 chemokine receptor. CX(3)CR1(+) CD8alpha(+) DC lack hallmarks of classical CD8alpha(+) DC, including IL-12 secretion, the capacity to cross-present antigen, and their developmental dependence on the transcriptional factor BatF3. Gene-expression profiling showed that CX(3)CR1(+) CD8alpha(+) DC resemble CD8alpha(-) cDC. The microarray analysis further revealed a unique plasmacytoid DC (PDC) gene signature of CX(3)CR1(+) CD8alpha(+) DC. A PDC relationship of the cells is supported further by the fact that they harbor characteristic D-J Ig gene rearrangements and that development of CX(3)CR1(+) CD8alpha(+) DC requires E2-2, the critical transcriptional regulator of PDC. Thus, CX(3)CR1(+) CD8alpha(+) DC represent a unique DC subset, related to but distinct from PDC. Collectively, the expression-profiling data of this study refine the resolution of previous DC definitions, sharpen the border of classical CD8alpha(+) and CD8alpha(-) DC, and should assist the identification of human counterparts of murine DC subsets.
Bar-On
Liat
L
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Birnberg
Tal
T
Lewis
Kanako L
KL
Edelson
Brian T
BT
Bruder
Dunja
D
Hildner
Kai
K
Buer
Jan
J
Murphy
Kenneth M
KM
Reizis
Boris
B
Jung
Steffen
S
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D016130:Immunophenotyping; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015728:Receptors, HIV / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D050976:Basic-Leucine Zipper Transcription Factors; D016827:CD8 Antigens; D000073883:CX3C Chemokine Receptor 1; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D012097:Repressor Proteins; C533289:SNFT protein, mouse; D049452:Green Fluorescent Proteins