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

• DOI: 10.1084/jem.194.7.1013
• Publication Date: 2002-07-26T16:48:33Z
• Authors: Mansour Mohamadzadeh; Frederic Berard; Gregory Essert; Cecile Chalouni; Bali Pulendran; Jean Davoust; George Bridges; A. Karolina Palucka; Jacques Banchereau
• Keywords: Interleukin-15; Antigen Presentation; Granulocyte-Macrophage Colony-Stimulating Factor; Cell Differentiation; Dendritic Cells; Monocytes; 03 medical and health sciences; Phenotype; 0302 clinical medicine; Epidermal Cells; Langerhans Cells; Humans; Epidermis; Lymphocyte Culture Test, Mixed

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.