Modular expression analysis reveals functional conservation between human Langerhans cells and mouse cross-priming dendritic cells.
Characterization of functionally distinct dendritic cell (DC) subsets in mice has fueled interest in whether analogous counterparts exist in humans. Transcriptional modules of coordinately expressed genes were used for defining shared functions between the species. Comparing modules derived from four human skin DC subsets and modules derived from the Immunological Genome Project database for all mouse DC subsets revealed that human Langerhans cells (LCs) and the mouse XCR1(+)CD8α(+)CD103(+) DCs shared the class I-mediated antigen processing and cross-presentation transcriptional modules that were not seen in mouse LCs. Furthermore, human LCs were enriched in a transcriptional signature specific to the blood cross-presenting CD141/BDCA-3(+) DCs, the proposed equivalent to mouse CD8α(+) DCs. Consistent with our analysis, LCs were highly adept at inducing primary CTL responses. Thus, our study suggests that the function of LCs may not be conserved between mouse and human and supports human LCs as an especially relevant therapeutic target.
Department of Pathology and Immunology and Department of Surgery/Plastic and Reconstructive Surgery Center, Washington University School of Medicine, St. Louis, MO 63110.
Maxim N
MN
Artyomov
Department of Pathology and Immunology and Department of Surgery/Plastic and Reconstructive Surgery Center, Washington University School of Medicine, St. Louis, MO 63110.
Adiel
A
Munk
Department of Pathology and Immunology and Department of Surgery/Plastic and Reconstructive Surgery Center, Washington University School of Medicine, St. Louis, MO 63110.
Laurent
L
Gorvel
Department of Pathology and Immunology and Department of Surgery/Plastic and Reconstructive Surgery Center, Washington University School of Medicine, St. Louis, MO 63110.
Daniel
D
Korenfeld
Department of Pathology and Immunology and Department of Surgery/Plastic and Reconstructive Surgery Center, Washington University School of Medicine, St. Louis, MO 63110.
Marina
M
Cella
Department of Pathology and Immunology and Department of Surgery/Plastic and Reconstructive Surgery Center, Washington University School of Medicine, St. Louis, MO 63110.
Thomas
T
Tung
Department of Pathology and Immunology and Department of Surgery/Plastic and Reconstructive Surgery Center, Washington University School of Medicine, St. Louis, MO 63110 eklechevsky@path.wustl.edu.
Eynav
E
Klechevsky
D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D000943:Antigens, Differentiation / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D012867:Skin / Q000166:cytology / Q000276:immunology*
D000943:Antigens, Differentiation