High-Dimensional Phenotypic Mapping of Human Dendritic Cells Reveals Interindividual Variation and Tissue Specialization

Immunity. 2017 Dec 19;47(6):1037-1050.e6. doi: 10.1016/j.immuni.2017.11.001. Epub 2017 Dec 5.

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.

Keywords: Axl+ dendritic cells; C-type lectins; CyTOF; antibody targeting; dendritic cells; human; interindividual variation; plasmacytoid dendritic cells; subsets; tissue specialization.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Monoclonal / pharmacokinetics
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / immunology*
  • Biological Variation, Individual*
  • Biomarkers / analysis
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / biosynthesis
  • Cytophotometry / methods
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Female
  • Gene Expression
  • Humans
  • Immunophenotyping
  • Immunotherapy
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred C57BL
  • Molecular Targeted Therapy
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Organ Specificity
  • Palatine Tonsil / cytology
  • Palatine Tonsil / immunology
  • Phenotype*
  • 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, Immunologic / genetics
  • Receptors, Immunologic / immunology*
  • Skin / cytology
  • Skin / immunology*
  • Spleen / cytology
  • Spleen / immunology

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation
  • Biomarkers
  • Cancer Vaccines
  • Proto-Oncogene Proteins
  • Receptors, Immunologic
  • SIRPA protein, human
  • Receptor Protein-Tyrosine Kinases
  • axl receptor tyrosine kinase