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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0900474v1 183/4/2242    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Duraisingham, S. S. Articles by Patterson, S. PubMed PubMed Citation Articles by Duraisingham, S. S. Articles by Patterson, S.

TLR-Stimulated CD34 Stem Cell-Derived Human Skin-Like and Monocyte-Derived Dendritic Cells Fail to Induce Th17 Polarization of Naive T Cells but Do Stimulate Th1 and Th17 Memory Responses¹

Department of Immunology, Faculty of Medicine, Imperial College, Chelsea and Westminster Hospital, London, United Kingdom

Dendritic cells (DCs) are important in linking innate and adaptive immune responses by priming and polarizing naive CD4⁺ Th cells, but little is known about the effect of different human DC subsets on Th cells, particularly Th17 cells. We have investigated the ability of TLR-stimulated human Langerhans cells (LC), dermal DCs (dDC), and monocyte-derived DCs (moDC) to affect naive and memory Th17 and Th1 responses. MoDCs stimulated greater memory T cell proliferation while LCs and dDCs more potently stimulated naive T cell proliferation, indicating functionally distinct subsets of DCs. TLR stimulation of all three DC types was unable to induce Th17 polarization from naive T cell precursors, despite inducing Th1 polarization. Dectin stimulation of DCs in IMDM was however able to produce Th17 cells. TLR-stimulated DCs were capable of inducing IL-17A and IFN- production from memory T cells, although the mechanism used by each DC subset differed. MoDCs partially mediated this effect on memory Th1 and Th17 cells by the production of soluble factors, which correlated with their ability to secrete IL-12p70 and IL-23. In contrast, LCs and dDCs were able to elicit a similar memory response to moDCs, but in a contact dependent manner. Additionally, the influence of microbial stimulation was demonstrated with TLR3 and TLR7/8 agonists inducing a Th1 response, whereas TLR2 or dectin stimulation of moDCs enhanced the IL-17 response. This study emphasizes the differences between human DC subsets and demonstrates that both the DC subset and the microbial stimulus influence the Th cell response.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by United Kingdom Medical Research Council and Europrise Consortium.

² Address correspondence and reprint requests to Dr. Steven Patterson, Department of Immunology, Faculty of Medicine, Imperial College, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, United Kingdom. E-mail address: s.patterson{at}imperial.ac.uk

³ Abbreviations used in this paper: DC, dendritic cell; LC, Langerhans cell; dDC, dermal DC; moDC, monocyte-derived DC; DC-SIGN, DC-specific intracellular adhesion molecule 3-grabbing nonintegrin.

⁴ The online version of this article contains supplemental material.