PMID- 19625644 OWN - NLM STAT- MEDLINE DCOM- 20090909 LR - 20211028 IS - 1550-6606 (Electronic) IS - 0022-1767 (Linking) VI - 183 IP - 4 DP - 2009 Aug 15 TI - 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 responses. PG - 2242-51 LID - 10.4049/jimmunol.0900474 [doi] AB - 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-gamma 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. FAU - Duraisingham, Sai Suda AU - Duraisingham SS AD - Department of Immunology, Faculty of Medicine, Imperial College, Chelsea and Westminster Hospital, London, United Kingdom. FAU - Hornig, Julia AU - Hornig J FAU - Gotch, Frances AU - Gotch F FAU - Patterson, Steven AU - Patterson S LA - eng GR - G0100482/MRC_/Medical Research Council/United Kingdom GR - G0501957/MRC_/Medical Research Council/United Kingdom PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090722 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Antigens, CD34) RN - 0 (Interleukin-17) RN - 0 (Receptors, Antigen, T-Cell) SB - IM MH - Adult MH - Antigens, CD34/biosynthesis MH - Cell Differentiation/immunology MH - Cell Polarity/immunology MH - Cells, Cultured MH - Dendritic Cells/classification/*immunology/metabolism MH - Female MH - Fetal Blood/cytology/immunology/metabolism MH - Humans MH - *Immunologic Memory MH - Interleukin-17/*biosynthesis/metabolism MH - Lymphocyte Activation/*immunology MH - Monocytes/immunology/metabolism MH - Receptors, Antigen, T-Cell/agonists/biosynthesis/*physiology MH - Resting Phase, Cell Cycle/immunology MH - Skin/cytology/*immunology MH - Stem Cells/*immunology/metabolism MH - T-Lymphocytes, Helper-Inducer/cytology/immunology MH - Th1 Cells/cytology/*immunology MH - Th2 Cells/cytology/immunology EDAT- 2009/07/25 09:00 MHDA- 2009/09/10 06:00 CRDT- 2009/07/24 09:00 PHST- 2009/07/24 09:00 [entrez] PHST- 2009/07/25 09:00 [pubmed] PHST- 2009/09/10 06:00 [medline] AID - jimmunol.0900474 [pii] AID - 10.4049/jimmunol.0900474 [doi] PST - ppublish SO - J Immunol. 2009 Aug 15;183(4):2242-51. doi: 10.4049/jimmunol.0900474. Epub 2009 Jul 22.