Transcriptional and Functional Analysis of CD1c + Human Dendritic Cells Identifies a CD163 + Subset Priming CD8 + CD103 + T Cells

Immunity. 2020 Aug 18;53(2):335-352.e8. doi: 10.1016/j.immuni.2020.06.002. Epub 2020 Jun 30.

Abstract

Dendritic cells (DCs) are antigen-presenting cells controlling T cell activation. In humans, the diversity, ontogeny, and functional capabilities of DC subsets are not fully understood. Here, we identified circulating CD88-CD1c+CD163+ DCs (called DC3s) as immediate precursors of inflammatory CD88-CD14+CD1c+CD163+FcεRI+ DCs. DC3s develop via a specific pathway activated by GM-CSF, independent of cDC-restricted (CDP) and monocyte-restricted (cMoP) progenitors. Like classical DCs but unlike monocytes, DC3s drove activation of naive T cells. In vitro, DC3s displayed a distinctive ability to prime CD8+ T cells expressing a tissue homing signature and the epithelial homing alpha-E integrin (CD103) through transforming growth factor β (TGF-β) signaling. In vivo, DC3s infiltrated luminal breast cancer primary tumors, and DC3 infiltration correlated positively with CD8+CD103+CD69+ tissue-resident memory T cells. Together, these findings define DC3s as a lineage of inflammatory DCs endowed with a strong potential to regulate tumor immunity.

Keywords: DC progenitors; DC3s; T(RM); cDC2s; conventional DCs; inflammatory DCs; monocytes; mononuclear phagocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism*
  • Antigens, CD1 / metabolism*
  • Antigens, Differentiation, Myelomonocytic / metabolism*
  • Breast Neoplasms / immunology*
  • CD8 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation / immunology
  • Cell Line, Tumor
  • Dendritic Cells / immunology*
  • Glycoproteins / metabolism*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Integrin alpha Chains / metabolism*
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred NOD
  • Receptors, Cell Surface / metabolism*
  • Transforming Growth Factor beta1 / metabolism
  • fms-Like Tyrosine Kinase 3 / metabolism

Substances

  • Antigens, CD
  • Antigens, CD1
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • CD1C protein, human
  • CD8 Antigens
  • CSF2 protein, human
  • Glycoproteins
  • Integrin alpha Chains
  • Receptors, Cell Surface
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • alpha E integrins
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3