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

Heger L, Hatscher L, Liang C, Lehmann C, Amon L, Lühr JJ, Kaszubowski T, Nzirorera R, Schaft N, Dörrie J, Irrgang P, Tenbusch M, Kunz M, Socher E, Autenrieth SE, Purbojo A, Sirbu H, Hartmann A, Alexiou C, Cesnjevar R, Dudziak D (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Proceedings of the National Academy of Sciences of the United States of America National Academy of Sciences

Book Volume: 120

Pages Range: e2300343120

Journal Issue: 33

DOI: 10.1073/pnas.2300343120

Abstract

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.

Authors with CRIS profile

Lukas Heger Department of Dermatology Lukas Hatscher Professur für die Biologie Dendritischer Zellen Christian Lehmann Department of Dermatology Lukas Amon Department of Dermatology Tomasz Kaszubowski Department of Dermatology Rayk Nzirorera Professur für die Biologie Dendritischer Zellen Niels Schaft Department of Dermatology Jan Dörrie Department of Dermatology Matthias Tenbusch Professur für Genbasierte Immunisierungsverfahren Meik Kunz Lehrstuhl für Medizinische Informatik Eileen Socher Lehrstuhl für Funktionelle und Klinische Anatomie Ariawan Purbojo Department of Paediatric Cardiac Surgery Horia Sirbu Professur für Thoraxchirurgie Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Christoph Alexiou Medizinische Fakultät Robert Cesnjevar Professur für Herzchirurgie mit dem Schwerpunkt Kinderherzchirurgie Diana Dudziak Professur für die Biologie Dendritischer Zellen

Involved external institutions

Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Max-Planck-Institut für die Physik des Lichts (MPL) / Max Planck Institute for the Science of Light DE Germany (DE)

How to cite

APA:

Heger, L., Hatscher, L., Liang, C., Lehmann, C., Amon, L., Lühr, J.J.,... Dudziak, D. (2023). XCR1 expression distinguishes human conventional dendritic cell type 1 with full effector functions from their immediate precursors. Proceedings of the National Academy of Sciences of the United States of America, 120(33), e2300343120. https://doi.org/10.1073/pnas.2300343120

MLA:

Heger, Lukas, et al. "XCR1 expression distinguishes human conventional dendritic cell type 1 with full effector functions from their immediate precursors." Proceedings of the National Academy of Sciences of the United States of America 120.33 (2023): e2300343120.

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