TY  - JOUR
AU  - Heger, Lukas
AU  - Hatscher, Lukas
AU  - Liang, Chunguang
AU  - Lehmann, Christian H K
AU  - Amon, Lukas
AU  - Lühr, Jennifer J
AU  - Kaszubowski, Tomasz
AU  - Nzirorera, Rayk
AU  - Schaft, Niels
AU  - Dörrie, Jan
AU  - Irrgang, Pascal
AU  - Tenbusch, Matthias
AU  - Kunz, Meik
AU  - Socher, Eileen
AU  - Autenrieth, Stella E
AU  - Purbojo, Ariawan
AU  - Sirbu, Horia
AU  - Hartmann, Arndt
AU  - Alexiou, Christoph
AU  - Cesnjevar, Robert
AU  - Dudziak, Diana
TI  - XCR1 expression distinguishes human conventional dendritic cell type 1 with full effector functions from their immediate precursors.
JO  - Proceedings of the National Academy of Sciences of the United States of America
VL  - 120
IS  - 33
SN  - 0027-8424
CY  - Washington, DC
PB  - National Acad. of Sciences
M1  - DKFZ-2023-01629
SP  - e2300343120
PY  - 2023
AB  - 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.
KW  - DC differentiation (Other)
KW  - IL-12 (Other)
KW  - XCR1 (Other)
KW  - antiviral immunity (Other)
KW  - cDC1 (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37566635
DO  - DOI:10.1073/pnas.2300343120
UR  - https://inrepo02.dkfz.de/record/278395
ER  -