Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, 91052 Erlangen, Germany.
Chair of Medical Informatics, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91058 Erlangen, Germany.
Proc Natl Acad Sci U S A. 2023 Aug 15;120(33):e2300343120. doi: 10.1073/pnas.2300343120. Epub 2023 Aug 11.
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.
树突状细胞 (DCs) 是先天和适应性免疫反应的主要调节者。DC 可分为浆细胞样 DC 和传统 DC (cDC) 1 型和 2 型。鼠类和人类 cDC1 共享 XCR1 的 mRNA 表达。鼠类研究表明，XCR1-XCL1 轴在免疫反应的诱导中具有特定作用。在这里，我们描述了人类 cDC1 可以在淋巴组织和非淋巴组织中分为 XCR1 和 XCR1 cDC1。与 XCR1 cDC1 相比，稳态 XCR1 cDC1 显示出预先激活的表型。刺激后，XCR1 cDC1 而非 XCR1 cDC1 分泌高水平的炎症细胞因子和趋化因子。这与 XCR1 cDC1 介导的 NK 细胞的激活增强有关。此外，XCR1 cDC1 在抑制甲型流感病毒复制方面表现出色。此外，在 DC 分化条件下，XCR1 cDC1 发育成 XCR1 cDC1。获得 XCR1 表达后，XCR1 cDC1 分泌相当水平的炎症细胞因子。因此，XCR1 是终末分化的 cDC1 的标志物，赋予人类 cDC1 的抗病毒效应功能，而 XCR1 cDC1 似乎代表 cDC1 的晚期即刻前体。
