XCR1 Expression Distinguishes Human Conventional Dendritic Cell Type 1 with Full Effector Functions from Their Immediate Precursors

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2023 Aug 11

PMID 37566635

Authors

Lukas Heger

Lukas Hatscher

Chunguang Liang

Christian H K Lehmann

Lukas Amon

Jennifer J Luhr

Tomasz Kaszubowski

Rayk Nzirorera

Niels Schaft

Jan Dorrie

Pascal Irrgang

Matthias Tenbusch

Meik Kunz

Eileen Socher

Stella E Autenrieth

Ariawan Purbojo

Horia Sirbu

Arndt Hartmann

Christoph Alexiou

Robert Cesnjevar

Diana Dudziak

Affiliations

Soon will be listed here.

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.

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