Interleukin 15 skews monocyte differentiation into dendritic cells with features of Langerhans cells.
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-2Rgamma 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)-3alpha/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.
Mohamadzadeh
M
M
Baylor Institute for Immunology Research, Baylor University Medical Center, Dallas, TX 75204, USA. mansourz@baylordallas.edu
Berard
F
F
Essert
G
G
Chalouni
C
C
Pulendran
B
B
Davoust
J
J
Bridges
G
G
Palucka
A K
AK
Banchereau
J
J
D017951:Antigen Presentation; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000145:classification / Q000166:cytology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology*; D007801:Langerhans Cells / Q000145:classification / Q000166:cytology*; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects*; D010641:Phenotype
D019409:Interleukin-15; D016178:Granulocyte-Macrophage Colony-Stimulating Factor