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Article

In Vitro Induction of T Helper 17 Cells by Synergistic Activation of Human Monocyte-Derived Langerhans Cell-Like Cells with Bacterial Agonists

1
Institute of Molecular Biology and Bioinformatics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
2
Center for Anesthesiology and Intensive Care Medicine, Department of intensive Care, Medical Center Hamburg-Eppendorf (UKE), Martinistrasse 52, 20246 Hamburg, Germany
3
Department of Surgery and Vascular Surgery, Franziskus Krankenhaus Berlin, University Hospital of Charité Universitätsmedizin Berlin, Budapester Straße 15-19, 10787 Berlin, Germany
4
Department of Pesticides Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(6), 1367; https://doi.org/10.3390/ijms20061367
Received: 15 February 2019 / Revised: 5 March 2019 / Accepted: 8 March 2019 / Published: 19 March 2019
(This article belongs to the Special Issue Inflammatory Skin Conditions 2018)
In the case of epidermal barrier disruption, pathogens encounter skin-resident Langerhans cells (LCs) and are recognized by pathogen recognition receptors such as Toll-like receptors (TLRs). As the majority of microorganisms exhibit more than one TLR ligand, the mechanisms of subsequent T cell differentiation are complex and far from clear. In this study, we investigated combinatory effects on Th cell polarization by bacterial cell wall compounds peptidoglycan (PGN) and lipopolysaccharide (LPS) and by bacterial nucleic acid (DNA). Expression of maturation markers CD40, CD80, HLA-DR and CCR7 and the release of IL-1β, IL-6 and IL-23 was strongly enhanced by simultaneous exposure to PGN, LPS and DNA in LCs. As all these factors were potential Th17 driving cytokines, we investigated the potency of combinatory TLR stimuli to induce Th17 cells via LC activation. High amounts of IL-17A and IL-22, key cytokines of Th17 cells, were detected. By intracellular costaining of IL-17+T cells, IL-22 (Th17) and IL-22+ (immature Th17) cells were identified. Interestingly, one population of LPS stimulated cells skewed into IL-9+Th cells, and LPS synergized with PGN while inducing high IL-22. In conclusion, our data indicates that when mediated by a fine-tuned signal integration via LCs, bacterial TLR agonists synergize and induce Th17 differentiation. View Full-Text
Keywords: Toll-like receptor; skin immune system; dendritic cells; T helper cell; Th17; IL-17; IL-22; IL-9 Toll-like receptor; skin immune system; dendritic cells; T helper cell; Th17; IL-17; IL-22; IL-9
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MDPI and ACS Style

Gramlich, R.; Aliahmadi, E.; Peiser, M. In Vitro Induction of T Helper 17 Cells by Synergistic Activation of Human Monocyte-Derived Langerhans Cell-Like Cells with Bacterial Agonists. Int. J. Mol. Sci. 2019, 20, 1367. https://doi.org/10.3390/ijms20061367

AMA Style

Gramlich R, Aliahmadi E, Peiser M. In Vitro Induction of T Helper 17 Cells by Synergistic Activation of Human Monocyte-Derived Langerhans Cell-Like Cells with Bacterial Agonists. International Journal of Molecular Sciences. 2019; 20(6):1367. https://doi.org/10.3390/ijms20061367

Chicago/Turabian Style

Gramlich, Robert, Ehsan Aliahmadi, and Matthias Peiser. 2019. "In Vitro Induction of T Helper 17 Cells by Synergistic Activation of Human Monocyte-Derived Langerhans Cell-Like Cells with Bacterial Agonists" International Journal of Molecular Sciences 20, no. 6: 1367. https://doi.org/10.3390/ijms20061367

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