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

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.