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Human Langerhans cells selectively activated via Toll‐like receptor 2 agonists acquire migratory and CD4 + T cell stimulatory capacity
Author(s) -
Peiser Matthias,
Koeck Juliana,
Kirschning Carsten J.,
Wittig Burghardt,
Wanner Reinhard
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0807567
Subject(s) - tlr2 , ccl19 , biology , microbiology and biotechnology , toll like receptor , cd86 , tlr3 , chemokine , dendritic cell , langerin , receptor , immune system , chemokine receptor , t cell , innate immune system , immunology , signal transduction , tlr4 , biochemistry
In epidermal Langerhans cells (LCs), the expression pattern and the functions of TLRs have been poorly characterized. By using mAb, we show that LCs from human skin express TLR1, ‐2, ‐5, ‐6, and ‐9, the cognate receptors for detection of specific bacteria‐derived molecules. As compared with other TLR agonists, LCs acquired a more matured phenotype when activated by specific bacterial or synthetic TLR2 agonists. In addition, monocyte‐derived Langerin + /CD1c + LCs (CD1c + MoLCs) secreted higher amounts of IL‐6 and TNF‐α by stimulation via TLR2 than by stimulation via TLR3, ‐4, ‐5, ‐8, and ‐9. In contrast to MoLCs, dendritic cells, generated from the same donor monocytes, were activated by agonists of TLRs other than TLR2 as well. Lipopeptides triggering TLR2 induced IL‐1R‐associated kinase‐1 phosphorylation and migration toward the chemokines CCL19 and CCL21 in epidermal LCs and CD1c + MoLCs. Up‐regulation of CD86, CD83, and CCR7, TNF‐α and IL‐6, and NF‐κB activation and proliferation of CD4 + T cells could be inhibited TLR2‐specific blockage using antibodies prior to TLR2 activation. Application of anti‐TLR1, anti‐TLR6, and anti‐TLR2 indicated an exclusive role of TLR2 in IL‐6 induction in human LCs. Collectively, our results show that TLR2 expressed by LCs mediates inflammatory responses to lipopeptides, which implicates a central role in sensing pathogens in human skin.