Immunity (Cambridge, Mass.), 2017-12, Vol.47 (6), p.1037-1050.e6
2017
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- Autor(en) / Beteiligte
- Titel
- High-Dimensional Phenotypic Mapping of Human Dendritic Cells Reveals Interindividual Variation and Tissue Specialization
- Ist Teil von
- Immunity (Cambridge, Mass.), 2017-12, Vol.47 (6), p.1037-1050.e6
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Given the limited efficacy of clinical approaches that rely on ex vivo generated dendritic cells (DCs), it is imperative to design strategies that harness specialized DC subsets in situ. This requires delineating the expression of surface markers by DC subsets among individuals and tissues. Here, we performed a multiparametric phenotypic characterization and unbiased analysis of human DC subsets in blood, tonsil, spleen, and skin. We uncovered previously unreported phenotypic heterogeneity of human cDC2s among individuals, including variable expression of functional receptors such as CD172a. We found marked differences in DC subsets localized in blood and lymphoid tissues versus skin, and a striking absence of the newly discovered Axl+ DCs in the skin. Finally, we evaluated the capacity of anti-receptor monoclonal antibodies to deliver vaccine components to skin DC subsets. These results offer a promising path for developing DC subset-specific immunotherapies that cannot be provided by transcriptomic analysis alone. [Display omitted] •CyTOF reveals interindividual heterogeneity among DC subsets, especially cDC2s•Human skin harbors cDCs with a unique phenotype and lacks Axl+ DCs•Axl+ DCs display phenotypic and functional diversity, and pDCs exhibit plasticity•Receptor profiling identifies targets for antigen delivery to skin DC subsets Dendritic cells (DCs) are potent initiators of immune responses; however, human DC subsets have yet to be successfully harnessed for immunotherapies. By combining CyTOF and unbiased analysis, Alcántara-Hernández et al. profile the heterogeneity of human DC subsets among individuals and tissues, providing comprehensive insights for the development of DC-based therapeutics.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1074-7613eISSN: 1097-4180DOI: 10.1016/j.immuni.2017.11.001Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5738280
- Format
- –
- Schlagworte
- Animals, Antibodies, Monoclonal - chemistry, Antibodies, Monoclonal - metabolism, Antibodies, Monoclonal - pharmacokinetics, antibody targeting, Antigens, CD - genetics, Antigens, CD - immunology, Antigens, Differentiation - genetics, Antigens, Differentiation - immunology, Axl protein, Axl+ dendritic cells, Biological Variation, Individual, Biomarkers - analysis, Blood, C-type lectins, Cancer Vaccines - administration & dosage, Cancer Vaccines - biosynthesis, Cells, CyTOF, Cytophotometry - methods, Dendritic cells, Dendritic Cells - cytology, Dendritic Cells - immunology, Drug delivery systems, Female, Gene Expression, Genotype & phenotype, human, Humans, Immunophenotyping, Immunotherapy, interindividual variation, Lymph Nodes - cytology, Lymph Nodes - immunology, Lymphoid tissue, Mice, Mice, Inbred C57BL, Molecular Targeted Therapy, Monoclonal antibodies, Neoplasms - genetics, Neoplasms - immunology, Neoplasms - pathology, Neoplasms - therapy, Organ Specificity, Palatine Tonsil - cytology, Palatine Tonsil - immunology, Phenotype, plasmacytoid dendritic cells, Proto-Oncogene Proteins - deficiency, Proto-Oncogene Proteins - genetics, Proto-Oncogene Proteins - immunology, Receptor Protein-Tyrosine Kinases - deficiency, Receptor Protein-Tyrosine Kinases - genetics, Receptor Protein-Tyrosine Kinases - immunology, Receptors, Receptors, Immunologic - genetics, Receptors, Immunologic - immunology, Skin, Skin - cytology, Skin - immunology, Specialization, Spleen, Spleen - cytology, Spleen - immunology, subsets, Surface markers, tissue specialization, Tissues, Tonsil