Interleukin 15 skews monocyte differentiation into dendritic cells with features of langerhans cells

M. Mohamadzadeh, F. Berard, G. Essert, C. Chalouni, B. Pulendran, J. Davoust, G. Bridges, A. K. Palucka, J. Banchereau

Research output: Contribution to journalArticlepeer-review

234 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1013-1019
Number of pages7
JournalJournal of Experimental Medicine
Volume194
Issue number7
DOIs
StatePublished - Oct 1 2001
Externally publishedYes

Keywords

  • Dendritic cells
  • Gamma chain
  • Interleukin 15
  • Langerhans cells
  • Monocytes

ASJC Scopus subject areas

  • Medicine(all)

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