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

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.