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024 7 _ |a 10.1073/pnas.2300343120
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024 7 _ |a 1091-6490
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037 _ _ |a DKFZ-2023-01629
041 _ _ |a English
082 _ _ |a 500
100 1 _ |a Heger, Lukas
|0 0000-0001-5591-2187
|b 0
245 _ _ |a XCR1 expression distinguishes human conventional dendritic cell type 1 with full effector functions from their immediate precursors.
260 _ _ |a Washington, DC
|c 2023
|b National Acad. of Sciences
336 7 _ |a article
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520 _ _ |a 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.
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650 _ 7 |a DC differentiation
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650 _ 7 |a IL-12
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650 _ 7 |a XCR1
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650 _ 7 |a antiviral immunity
|2 Other
650 _ 7 |a cDC1
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700 1 _ |a Hatscher, Lukas
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700 1 _ |a Liang, Chunguang
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700 1 _ |a Lehmann, Christian H K
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700 1 _ |a Amon, Lukas
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700 1 _ |a Lühr, Jennifer J
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700 1 _ |a Kaszubowski, Tomasz
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700 1 _ |a Nzirorera, Rayk
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700 1 _ |a Schaft, Niels
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700 1 _ |a Dörrie, Jan
|0 0000-0002-3478-0741
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700 1 _ |a Irrgang, Pascal
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700 1 _ |a Tenbusch, Matthias
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700 1 _ |a Kunz, Meik
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700 1 _ |a Socher, Eileen
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700 1 _ |a Autenrieth, Stella E
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700 1 _ |a Purbojo, Ariawan
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700 1 _ |a Sirbu, Horia
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700 1 _ |a Hartmann, Arndt
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700 1 _ |a Alexiou, Christoph
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700 1 _ |a Cesnjevar, Robert
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700 1 _ |a Dudziak, Diana
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773 _ _ |a 10.1073/pnas.2300343120
|g Vol. 120, no. 33, p. e2300343120
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|n 33
|p e2300343120
|t Proceedings of the National Academy of Sciences of the United States of America
|v 120
|y 2023
|x 0027-8424
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