학술논문

High-Dimensional Phenotypic Mapping of Human Dendritic Cells Reveals Interindividual Variation and Tissue Specialization
Document Type
article
Source
Immunity. 47(6)
Subject
Biomedical and Clinical Sciences
Immunology
Prevention
Biotechnology
Immunization
Emerging Infectious Diseases
Vaccine Related
Good Health and Well Being
Animals
Antibodies
Monoclonal
Antigens
CD
Antigens
Differentiation
Biological Variation
Individual
Biomarkers
Cancer Vaccines
Cytophotometry
Dendritic Cells
Female
Gene Expression
Humans
Immunophenotyping
Immunotherapy
Lymph Nodes
Mice
Mice
Inbred C57BL
Molecular Targeted Therapy
Neoplasms
Organ Specificity
Palatine Tonsil
Phenotype
Proto-Oncogene Proteins
Receptor Protein-Tyrosine Kinases
Receptors
Immunologic
Skin
Spleen
Axl Receptor Tyrosine Kinase
Axl+ dendritic cells
C-type lectins
CyTOF
antibody targeting
dendritic cells
human
interindividual variation
plasmacytoid dendritic cells
subsets
tissue specialization
Language
Abstract
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.