The Journal of Experimental Medicine
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Published online 1 October 2001. doi:10.1084/jem.194.7.1013
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© The Rockefeller University Press, 0022-1007/2001/10/1013/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 7, October 1, 2001 1013-1020

Brief Definitive Report

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

Mansour Mohamadzadeha, Frederic Berarda, Gregory Esserta, Cecile Chalounia, Bali Pulendrana, Jean Davousta, George Bridgesb, A. Karolina Paluckaa, and Jacques Banchereaua

a Baylor Institute for Immunology Research, Baylor University Medical Center, Dallas, TX 75204
b Department of Pathology, Baylor University Medical Center, Dallas, TX 75204
Baylor Institute for Immunology Research, 3434 Live Oak, Dallas, TX 75204.214-820-4813214-820-9969

mansourz{at}baylordallas.edu

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-2R{gamma} 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){alpha}, 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)-3{alpha}/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.

Key Words: monocytes • dendritic cells • Langerhans cells • interleukin 15 • gamma chain

M. Mohamadzadeh and F. Berard contributed equally to this work.

© 2001 The Rockefeller University Press


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