Interleukin 15 Skews Monocyte Differentiation into Dendritic Cells with Features of Langerhans Cells

Abstract

Langerhans cells (LCs) represent a subset of immature dendritic cells (DCs) specifically localized in the epidermis and other mucosal epithelia. As surrounding keratinocytes can produce interleukin (IL)-15, a cytokine that utilizes IL-2Rγ chain, we analyzed whether IL-15 could skew monocyte differentiation into LCs. Monocytes cultured for 6 d with granulocyte/macrophage colony-stimulating factor (GM-CSF) and IL-15 differentiate into CD1a+HLA-DR+CD14−DCs (IL15-DCs). Agents such as lipopolysaccharide (LPS), tumor necrosis factor (TNF)α, and CD40L induce maturation of IL15-DCs to CD83+, DC-LAMP+ cells. IL15-DCs are potent antigen-presenting cells able to induce the primary (mixed lymphocyte reaction [MLR]) and secondary (recall responses to flu-matrix peptide) immune responses. As opposed to cultures made with GM-CSF/IL-4 (IL4-DCs), a proportion of IL15-DCs expresses LC markers: E-Cadherin, Langerin, and CC chemokine receptor (CCR)6. Accordingly, IL15-DCs, but not IL4-DCs, migrate in response to macrophage inflammatory protein (MIP)-3α/CCL20. However, IL15-DCs cannot be qualified as “genuine” Langerhans cells because, despite the presence of the 43-kD Langerin, they do not express bona fide Birbeck granules. Thus, our results demonstrate a novel pathway in monocyte differentiation into dendritic cells.

TNF Skews Monocyte Differentiation from Macrophages to Dendritic Cells

“…We have previously shown that monocytes yield DCs with Langerhans cell (LCs) properties when cultured with GM-CSF and IL-15 (25). In this study, we show that in the presence of fibroblasts and TNF, monocytes yield CD1a ϩ DC-SIGN ϩ cells as well as a subset of cells expressing surface Langerin, a marker of LCs.…”

IL‐15‐induced human DC efficiently prime melanoma‐specific naive CD8+ T cells to differentiate into CTL

“…We and others have recently shown in mice the potency of IL-15-induced DC to generate OVA-specific immunity in vivo [30][31][32]. Furthermore, we showed that human IL15-DC were particularly efficient at activating Flu matrix peptide-specific memory CD8 + T cells [14]. The importance of the current work stems from the demonstration of efficient priming of CTL specific to self antigens expressed by tumor cells.…”

“…The value of this vaccine might be related to its composite nature as it consists of at least two DC subsets and most particularly Langerhans cells which have not been assessed in any other clinical trial to date. In this context, we reported that IL-15 together with GM-CSF induces monocytes to differentiate into cells with properties of Langerhans cells (IL15-DC) and the preferential ability to enhance CD8 + T cell proliferation [14]. We show here the efficiency of these cells to prime naive CD8 + T cells to differentiate into melanoma-specific CTL.…”

“…2a, Table 1). IL15-DC uniquely express Langerin, a surface marker of Langerhans cells (not shown and [14]). Activation with LPS induces a *10-fold increase in MHC class I and class II, CD80 and CD86 expression (Fig.…”

Dendritic cell targeting ofBacillus anthracisprotective antigen expressed byLactobacillus acidophilusprotects mice from lethal challenge

“…As a control, a portion of DCs were incubated with Alexa Fluor 647-labeled L. acidophilus strains on ice. These cells were then washed with cold PBS/0.1% FCS and analyzed by flow cytometry (45).…”