In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 33 ( 2023-08-15)
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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.2300343120
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2023
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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