Skin-Specific CD301bDermal Dendritic Cells Drive IL-17-Mediated Psoriasis-Like Immune Response in Mice.

Abstract

Conventional dendritic cells (cDCs) are composed of heterogeneous subsets commonly arising from dendritic cell (DC)-committed progenitors. A population of CD301b-expressing DCs has recently been identified in non-lymphoid barrier tissues such as skin. However, whether CD301bDCs in the skin represent an ontogenetically unique subpopulation of migratory cDCs has not been fully addressed. Here, we demonstrated that CD301bdermal DCs were distinct subpopulation of FMS-like tyrosine kinase 3 ligand (FLT3L)-dependent CD11bcDC2 lineage, which required an additional GM-CSF cue for the adequate development. Although the majority of lymphoid-resident cDC2 lacked CD301b expression, dermal migratory cDC2 contained a substantial fraction of CD301bsubset. Similar to CD301bpopulation, CD301bdermal DC development was closely regulated by FLT3 signaling, suggesting their common origin from FLT3L-responsive cDC progenitors. However, FLT3L-driven cDC progenitor culture was not sufficient, but additional GM-CSF treatment was required to produce CD301bcDC2. In vivo development of CD301bcDC2 was significantly augmented by exogenous GM-CSF, while the repopulation of CD301bdermal cDC2 was abrogated by GM-CSF neutralization. Functionally, CD301bcDC2 was capable of producing a high level of IL-23, and the depletion of CD301bcDC2 effectively prevented IL-17-mediated psoriasiform dermatitis. Therefore, our findings highlight the differentiation program of a distinct CD301bdermal cDC2 subset in the skin and its involvement in psoriatic inflammation.