A discrete population of IFN λ-expressing BDCA3hi dendritic cells is present in human thymus.

Human thymus contains two major subpopulations of dendritic cells (DCs), conventional DCs (cDCs) and plasmacytoid DCs (pDCs), which are mainly involved in central tolerance and also in protecting the thymus against infections. In blood and peripheral organs cDCs include the subpopulation of BDCA3(hi) DCs, considered as equivalents to mouse CD8α(+) DCs. In this study we describe in human thymus the presence of a discrete population of BDCA3(hi) DCs that, like their peripheral counterparts, express CD13, low-intermediate levels of CD11c, CLEC9A, high levels of XCR1, IRF8 and TLR3, and mostly lack the expression of CD11b, CD14 and TLR7. Thymic BDCA3(hi) DCs display immature features with a low expression of costimulatory molecules and HLA-DR, and a low allostimulatory capacity. Also, BDCA3(hi) DCs exhibit a strong response to TLR3 stimulation, producing high levels of interferon (IFN)-λ1 and CXCL10, which indicates that, similarly to thymic pDCs, BDCA3(hi) DCs can have an important role in thymus protection against viral infections.

Wnt5a signaling increases IL-12 secretion by human dendritic cells and enhances IFN-γ production by CD4+ T cells.

Wnt5a is a secreted pleiotropic glycoprotein produced in an inflammatory state by a wide spectrum of ubiquitous cell populations. Recently, we demonstrated that Wnt5a skews the differentiation of human monocyte derived dendritic cells (moDCs) to a tolerogenic functional state. In this study we focus our interest on the role of this Wnt ligand after DC differentiation, during their maturation and function. We show that the expression of Wnt receptors is tightly regulated during the life cycle of DCs suggesting a differential responsiveness to Wnt signaling conditioned by their differentiation stage and the maturational stimuli. Furthermore, we confirm that Wnt5a is the main non-canonical Wnt protein expressed by DCs and its production increases upon specific stimuli. Exogenous Wnt5a improved the endocytic capacity of immature DCs but it is not a stimulatory signal on its own, slightly affecting the maturation and function of DCs. However, knocking down Wnt5a gene expression in maturing DCs demonstrates that DC-derived Wnt5a is necessary for normal IL-12 secretion and plays a positive role during the development of Th1 responses. Wnt5a acts both in autocrine and paracrine ways. Thus, human naive CD4(+) T cells express Wnt receptors and, the addition of Wnt5a during CD3/CD28 stimulation enhances IL-2 and IFN-γ production. Taken together these results suggest a time-dependent role for Wnt5a during inflammatory responses conditioned by the differentiation stage of cellular targets.