Human Tissues Contain CD141hi Cross-Presenting Dendritic Cells with Functional Homology to Mouse CD103+ Nonlymphoid Dendritic Cells

• Published in: Immunity (Cambridge, Mass.) Vol. 37; no. 1; pp. 60 - 73
• Main Authors: Haniffa, Muzlifah, Shin, Amanda, Bigley, Venetia, McGovern, Naomi, Teo, Pearline, See, Peter, Wasan, Pavandip Singh, Wang, Xiao-Nong, Malinarich, Frano, Malleret, Benoit, Larbi, Anis, Tan, Pearlie, Zhao, Helen, Poidinger, Michael, Pagan, Sarah, Cookson, Sharon, Dickinson, Rachel, Dimmick, Ian, Jarrett, Ruth F., Renia, Laurent, Tam, John, Song, Colin, Connolly, John, Chan, Jerry K.Y., Gehring, Adam, Bertoletti, Antonio, Collin, Matthew, Ginhoux, Florent
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.07.2012; Elsevier Limited; Cell Press
• Subjects: Animals; Antigens - immunology; Antigens, CD - metabolism; Cell Movement - immunology; Chemokine CXCL10 - biosynthesis; Chemokines; Colleges & universities; Cross-Priming - immunology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Flow cytometry; Gene expression; Gene Expression Profiling; Humans; Immunophenotyping; Integrin alpha Chains - metabolism; Langerhans Cells - immunology; Langerhans Cells - metabolism; Lymph Nodes - immunology; Lymph Nodes - metabolism; Medical research; Mice; Population; Skin - immunology; Transcriptome; Tumor Necrosis Factor-alpha - biosynthesis; Tumors; Vaccines
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2012.04.012

Dendritic cell (DC)-mediated cross-presentation of exogenous antigens acquired in the periphery is critical for the initiation of CD8+ T cell responses. Several DC subsets are described in human tissues but migratory cross-presenting DCs have not been isolated, despite their potential importance in immunity to pathogens, vaccines, and tumors and tolerance to self. Here, we identified a CD141hi DC present in human interstitial dermis, liver, and lung that was distinct from the majority of CD1c+ and CD14+ tissue DCs and superior at cross-presenting soluble antigens. Cutaneous CD141hi DCs were closely related to blood CD141+ DCs, and migratory counterparts were found among skin-draining lymph node DCs. Comparative transcriptomic analysis with mouse showed tissue DC subsets to be conserved between species and permitted close alignment of human and mouse DC subsets. These studies inform the rational design of targeted immunotherapies and facilitate translation of mouse functional DC biology to the human setting. [Display omitted] ► Human tissues contain CD1c+ DCs, CD14+ DCs, and a CD141hi cross-presenting DC subset ► CD141hi DCs migrate to draining lymph nodes and probably arise from blood CD141+ DCs ► Human tissue CD141hi DCs are homologous to mouse CD103+ or CD8+ DCs ► Human tissue CD1c+ DCs are homologous to mouse CD4+ DCs