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Anaphylatoxin C5a Regulates 6-Sulfo-LacNAc Dendritic Cell Function in Human through Crosstalk with Toll-Like Receptor-Induced CREB Signaling

Activation of antigen-presenting dendritic cells (DCs) and the complement system are essential early events in the immune defense against invading pathogens. Recently, we and others demonstrated immunological crosstalk between signaling from receptors recognizing complement activation products and P...

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Autores principales: Zaal, Anouk, Dieker, Miranda, Oudenampsen, Manon, Turksma, Annelies W., Lissenberg-Thunnissen, Suzanne N., Wouters, Diana, van Ham, S. Marieke, ten Brinke, Anja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509794/
https://www.ncbi.nlm.nih.gov/pubmed/28769928
http://dx.doi.org/10.3389/fimmu.2017.00818
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author Zaal, Anouk
Dieker, Miranda
Oudenampsen, Manon
Turksma, Annelies W.
Lissenberg-Thunnissen, Suzanne N.
Wouters, Diana
van Ham, S. Marieke
ten Brinke, Anja
author_facet Zaal, Anouk
Dieker, Miranda
Oudenampsen, Manon
Turksma, Annelies W.
Lissenberg-Thunnissen, Suzanne N.
Wouters, Diana
van Ham, S. Marieke
ten Brinke, Anja
author_sort Zaal, Anouk
collection PubMed
description Activation of antigen-presenting dendritic cells (DCs) and the complement system are essential early events in the immune defense against invading pathogens. Recently, we and others demonstrated immunological crosstalk between signaling from receptors recognizing complement activation products and PAMPs on DCs. This affects DC effector function, as demonstrated by the finding that C5a prevents induction of pro-inflammatory cytokines by toll-like receptor (TLR) ligands in human monocyte-derived DCs (moDCs). Here, we demonstrate that this regulatory crosstalk is specifically important in 6-sulfo LacNAc dendritic cells (slanDCs), the most pro-inflammatory DC subset found in human. C5aR and TLR signaling show profound interference in the ERK/p38/CREB1 signaling pathways. C5aR signaling accelerates TLR-induced CREB1 phosphorylation both in moDC and slanDC. This is key in the regulatory effect of C5a on pro-inflammatory DC maturation by mediating induction of IL-10, which subsequently inhibits pro-inflammatory cytokine production via negative feedback signaling. Importantly, the regulatory effect of C5a affects T-cell immunity by decreasing Th1 and cytotoxic CD8 T-cell responses. The finding that the pro-inflammatory effector function of slanDC can be down modulated by activation products of the complement system highlights the existence of intricate regulatory interactions between various arms of the immune system. Intensive immune monitoring of patients suffering from complement-mediated diseases or patients receiving complement modulating compounds can give more inside in the contribution of complement receptor and TLR crosstalk in APCs in disease.
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spelling pubmed-55097942017-08-02 Anaphylatoxin C5a Regulates 6-Sulfo-LacNAc Dendritic Cell Function in Human through Crosstalk with Toll-Like Receptor-Induced CREB Signaling Zaal, Anouk Dieker, Miranda Oudenampsen, Manon Turksma, Annelies W. Lissenberg-Thunnissen, Suzanne N. Wouters, Diana van Ham, S. Marieke ten Brinke, Anja Front Immunol Immunology Activation of antigen-presenting dendritic cells (DCs) and the complement system are essential early events in the immune defense against invading pathogens. Recently, we and others demonstrated immunological crosstalk between signaling from receptors recognizing complement activation products and PAMPs on DCs. This affects DC effector function, as demonstrated by the finding that C5a prevents induction of pro-inflammatory cytokines by toll-like receptor (TLR) ligands in human monocyte-derived DCs (moDCs). Here, we demonstrate that this regulatory crosstalk is specifically important in 6-sulfo LacNAc dendritic cells (slanDCs), the most pro-inflammatory DC subset found in human. C5aR and TLR signaling show profound interference in the ERK/p38/CREB1 signaling pathways. C5aR signaling accelerates TLR-induced CREB1 phosphorylation both in moDC and slanDC. This is key in the regulatory effect of C5a on pro-inflammatory DC maturation by mediating induction of IL-10, which subsequently inhibits pro-inflammatory cytokine production via negative feedback signaling. Importantly, the regulatory effect of C5a affects T-cell immunity by decreasing Th1 and cytotoxic CD8 T-cell responses. The finding that the pro-inflammatory effector function of slanDC can be down modulated by activation products of the complement system highlights the existence of intricate regulatory interactions between various arms of the immune system. Intensive immune monitoring of patients suffering from complement-mediated diseases or patients receiving complement modulating compounds can give more inside in the contribution of complement receptor and TLR crosstalk in APCs in disease. Frontiers Media S.A. 2017-07-14 /pmc/articles/PMC5509794/ /pubmed/28769928 http://dx.doi.org/10.3389/fimmu.2017.00818 Text en Copyright © 2017 Zaal, Dieker, Oudenampsen, Turksma, Lissenberg-Thunnissen, Wouters, van Ham and ten Brinke. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zaal, Anouk
Dieker, Miranda
Oudenampsen, Manon
Turksma, Annelies W.
Lissenberg-Thunnissen, Suzanne N.
Wouters, Diana
van Ham, S. Marieke
ten Brinke, Anja
Anaphylatoxin C5a Regulates 6-Sulfo-LacNAc Dendritic Cell Function in Human through Crosstalk with Toll-Like Receptor-Induced CREB Signaling
title Anaphylatoxin C5a Regulates 6-Sulfo-LacNAc Dendritic Cell Function in Human through Crosstalk with Toll-Like Receptor-Induced CREB Signaling
title_full Anaphylatoxin C5a Regulates 6-Sulfo-LacNAc Dendritic Cell Function in Human through Crosstalk with Toll-Like Receptor-Induced CREB Signaling
title_fullStr Anaphylatoxin C5a Regulates 6-Sulfo-LacNAc Dendritic Cell Function in Human through Crosstalk with Toll-Like Receptor-Induced CREB Signaling
title_full_unstemmed Anaphylatoxin C5a Regulates 6-Sulfo-LacNAc Dendritic Cell Function in Human through Crosstalk with Toll-Like Receptor-Induced CREB Signaling
title_short Anaphylatoxin C5a Regulates 6-Sulfo-LacNAc Dendritic Cell Function in Human through Crosstalk with Toll-Like Receptor-Induced CREB Signaling
title_sort anaphylatoxin c5a regulates 6-sulfo-lacnac dendritic cell function in human through crosstalk with toll-like receptor-induced creb signaling
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509794/
https://www.ncbi.nlm.nih.gov/pubmed/28769928
http://dx.doi.org/10.3389/fimmu.2017.00818
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