Differential production of inflammatory chemokines by murine dendritic cell subsets

Abstract

Dendritic cells (DC) are efficient antigen presenting cells with the ability to activate naı̈ve T cells. Murine DC represent a heterogeneous population that can be subdivided into distinct subsets, including the conventional DC (cDC) which are either CD4 −CD8 − (DN), CD4 +CD8 − (CD4 +) or CD4 −CD8 + (CD8 +) subsets and the plasmacytoid DC (pDC), which have different immune regulatory functions. In this study, we investigated the differential expression of genes encoding the inflammatory chemokines Mip-1α, Mip-1β and Rantes, and the secretion of these chemokines, among splenic DC subsets. These chemokine genes were expressed at higher levels by the splenic CD4 + and DN cDC subsets compared with the CD8 + cDC, in both the resting and activated states in vivo. Both the pDC and cDC subsets displayed increases in chemokine secretion in response to a range of toll-like receptor (TLR) stimuli in vitro. Whilst the pDC were the highest producers of Mip-1α and Mip-1β in response to some TLR stimuli, the DN and CD4 + cDC subsets were the superior producers of Rantes. Overall, of the cDC, the CD4 + cDC produced all chemokines most efficiently, both at a basal level, and in response to most TLR stimuli. Thus, we report a new functional difference between the murine splenic cDC subsets, with the CD4 + cDC demonstrating the most efficient production of the inflammatory chemokines Mip-1α, Mip-1β and Rantes.