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.
Pierre Bourdely  1 ,  Giorgio Anselmi  1 ,  Kristine Vaivode  1 ,  Rodrigo Nalio Ramos  2 ,  Yoann Missolo-Koussou  2 ,  Sofia Hidalgo  3 ,  Jimena Tosselo  2 ,  Nicolas Nuñez  2 ,  Wilfrid Richer  2 ,  Anne Vincent-Salomon  4 ,  Alka Saxena  5 ,  Kristie Wood  5 ,  Alvaro Lladser  6 ,  Eliane Piaggio  2 ,  Julie Helft  2 ,  Pierre Guermonprez  7
Affiliations
  • 1. Centre for Inflammation Biology and Cancer Immunology, The Peter Gorer Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, London, UK; Cancer Research UK King's Health Partner Cancer Centre, King's College London, London, UK.
  • 2. PSL Research University, Institut Curie Research Center, Translational Immunotherapy Team, INSERM U932, Paris, France.
  • 3. PSL Research University, Institut Curie Research Center, Translational Immunotherapy Team, INSERM U932, Paris, France; Laboratory of Immuno-oncology, Fundación Ciencia & Vida, Santiago, Chile.
  • 4. PSL Research University, Institut Curie, Department of Biopathology, Paris, France.
  • 5. National Institute of Health Research Biomedical Research Centre at Guy's and St Thomas' Hospital and King's College London, London, UK.
  • 6. Laboratory of Immuno-oncology, Fundación Ciencia & Vida, Santiago, Chile; Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile.
  • 7. Centre for Inflammation Biology and Cancer Immunology, The Peter Gorer Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London, London, UK; Cancer Research UK King's Health Partner Cancer Centre, King's College London, London, UK; Université de Paris, Centre for Inflammation Research, CNRS ERL8252, INSERM1149 Paris, France. Electronic address: [email protected].
PMID: 32610077 DOI: 10.1016/j.immuni.2020.06.002
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.