XCR1 expression distinguishes human conventional dendritic cell type 1 with full effector functions from their immediate precursors

Dendritic cells (DCs) are major regulators of innate and adaptive immune responses. DCs can be classified into plasmacytoid DCs and conventional DCs (cDCs) type 1 and 2. Murine and human cDC1 share the mRNA expression of XCR1. Murine studies indicated a specific role of the XCR1-XCL1 axis in the ind...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2023-08, Vol.120 (33), p.e2300343120-e2300343120
Main Authors: Heger, Lukas, Hatscher, Lukas, Liang, Chunguang, Lehmann, Christian H K, Amon, Lukas, Lühr, Jennifer J, Kaszubowski, Tomasz, Nzirorera, Rayk, Schaft, Niels, Dörrie, Jan, Irrgang, Pascal, Tenbusch, Matthias, Kunz, Meik, Socher, Eileen, Autenrieth, Stella E, Purbojo, Ariawan, Sirbu, Horia, Hartmann, Arndt, Alexiou, Christoph, Cesnjevar, Robert, Dudziak, Diana
Format: Article
Language:English
Subjects:
Biological Sciences
Cell activation
Chemokines
Cytokines
Dendritic cells
Gene expression
Inflammation
Influenza A
Phenotypes
Precursors
Viruses
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Summary:Dendritic cells (DCs) are major regulators of innate and adaptive immune responses. DCs can be classified into plasmacytoid DCs and conventional DCs (cDCs) type 1 and 2. Murine and human cDC1 share the mRNA expression of XCR1. Murine studies indicated a specific role of the XCR1-XCL1 axis in the induction of immune responses. Here, we describe that human cDC1 can be distinguished into XCR1 and XCR1 cDC1 in lymphoid as well as nonlymphoid tissues. Steady-state XCR1 cDC1 display a preactivated phenotype compared to XCR1 cDC1. Upon stimulation, XCR1 cDC1, but not XCR1 cDC1, secreted high levels of inflammatory cytokines as well as chemokines. This was associated with enhanced activation of NK cells mediated by XCR1 cDC1. Moreover, XCR1 cDC1 excelled in inhibiting replication of Influenza A virus. Further, under DC differentiation conditions, XCR1 cDC1 developed into XCR1 cDC1. After acquisition of XCR1 expression, XCR1 cDC1 secreted comparable level of inflammatory cytokines. Thus, XCR1 is a marker of terminally differentiated cDC1 that licenses the antiviral effector functions of human cDC1, while XCR1 cDC1 seem to represent a late immediate precursor of cDC1.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2300343120