Transitional dendritic cells are distinct from conventional DC2 precursors and mediate proinflammatory antiviral responses

Fernando Bandeira Sulczewski; Raul A Maqueda-Alfaro; Marcela Alcántara-Hernández; Oriana A Perez; Sanjana Saravanan; Tae Jin Yun; David Seong; Rebeca Arroyo Hornero; Hayley M Raquer-McKay; Eduardo Esteva; Zachary R Lanzar; Rebecca A Leylek; Nicholas M Adams; Annesa Das; Adeeb H Rahman; Andres Gottfried-Blackmore; Boris Reizis; Juliana Idoyaga

doi:10.1038/s41590-023-01545-7

Transitional dendritic cells are distinct from conventional DC2 precursors and mediate proinflammatory antiviral responses

Nat Immunol. 2023 Aug;24(8):1265-1280. doi: 10.1038/s41590-023-01545-7. Epub 2023 Jul 6.

Authors

Fernando Bandeira Sulczewski^#^{1

2}, Raul A Maqueda-Alfaro^#^{1

2}, Marcela Alcántara-Hernández^#^{1

2}, Oriana A Perez³, Sanjana Saravanan^{1

2}, Tae Jin Yun³, David Seong^{1

2

4}, Rebeca Arroyo Hornero^{1

2}, Hayley M Raquer-McKay^{1

2}, Eduardo Esteva³, Zachary R Lanzar^{1

2}, Rebecca A Leylek^{1

2}, Nicholas M Adams³, Annesa Das³, Adeeb H Rahman^{5

6

7

8}, Andres Gottfried-Blackmore^{1

2

9}, Boris Reizis¹⁰, Juliana Idoyaga^{11

12}

Affiliations

¹ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
² Immunology Program, Stanford University School of Medicine, Stanford, CA, USA.
³ Department of Pathology, New York University Grossman School of Medicine, New York, NY, USA.
⁴ Medical Scientist Training Program, Stanford University School of Medicine, Stanford, CA, USA.
⁵ Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁶ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁷ The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁸ Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁹ Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Redwood City, CA, USA.
¹⁰ Department of Pathology, New York University Grossman School of Medicine, New York, NY, USA. [email protected].
¹¹ Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA. [email protected].
¹² Immunology Program, Stanford University School of Medicine, Stanford, CA, USA. [email protected].

^# Contributed equally.

Abstract

High-dimensional approaches have revealed heterogeneity amongst dendritic cells (DCs), including a population of transitional DCs (tDCs) in mice and humans. However, the origin and relationship of tDCs to other DC subsets has been unclear. Here we show that tDCs are distinct from other well-characterized DCs and conventional DC precursors (pre-cDCs). We demonstrate that tDCs originate from bone marrow progenitors shared with plasmacytoid DCs (pDCs). In the periphery, tDCs contribute to the pool of ESAM⁺ type 2 DCs (DC2s), and these DC2s have pDC-related developmental features. Different from pre-cDCs, tDCs have less turnover, capture antigen, respond to stimuli and activate antigen-specific naïve T cells, all characteristics of differentiated DCs. Different from pDCs, viral sensing by tDCs results in IL-1β secretion and fatal immune pathology in a murine coronavirus model. Our findings suggest that tDCs are a distinct pDC-related subset with a DC2 differentiation potential and unique proinflammatory function during viral infections.

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
Antiviral Agents
Bone Marrow* / immunology
Cell Differentiation
Dendritic Cells* / classification
Dendritic Cells* / immunology
Mice

Substances

Antiviral Agents
Esam protein, mouse

Abstract

Publication types

MeSH terms

Substances

Grants and funding