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Clec4A4 is a regulatory receptor for dendritic cells that impairs inflammation and T-cell immunity

Dendritic cells (DCs) comprise several subsets that are critically involved in the initiation and regulation of immunity. Clec4A4/DC immunoreceptor 2 (DCIR2) is a C-type lectin receptor (CLR) exclusively expressed on CD8α(−) conventional DCs (cDCs). However, how Clec4A4 controls immune responses thr...

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Autores principales: Uto, Tomofumi, Fukaya, Tomohiro, Takagi, Hideaki, Arimura, Keiichi, Nakamura, Takeshi, Kojima, Naoya, Malissen, Bernard, Sato, Katsuaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832068/
https://www.ncbi.nlm.nih.gov/pubmed/27068492
http://dx.doi.org/10.1038/ncomms11273
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author Uto, Tomofumi
Fukaya, Tomohiro
Takagi, Hideaki
Arimura, Keiichi
Nakamura, Takeshi
Kojima, Naoya
Malissen, Bernard
Sato, Katsuaki
author_facet Uto, Tomofumi
Fukaya, Tomohiro
Takagi, Hideaki
Arimura, Keiichi
Nakamura, Takeshi
Kojima, Naoya
Malissen, Bernard
Sato, Katsuaki
author_sort Uto, Tomofumi
collection PubMed
description Dendritic cells (DCs) comprise several subsets that are critically involved in the initiation and regulation of immunity. Clec4A4/DC immunoreceptor 2 (DCIR2) is a C-type lectin receptor (CLR) exclusively expressed on CD8α(−) conventional DCs (cDCs). However, how Clec4A4 controls immune responses through regulation of the function of CD8α(−) cDCs remains unclear. Here we show that Clec4A4 is a regulatory receptor for the activation of CD8α(−) cDCs that impairs inflammation and T-cell immunity. Clec4a4(−/−)CD8α(−) cDCs show enhanced cytokine production and T-cell priming following Toll-like receptor (TLR)-mediated activation. Furthermore, Clec4a4(−/−) mice exhibit TLR-mediated hyperinflammation. On antigenic immunization, Clec4a4(−/−) mice show not only augmented T-cell responses but also progressive autoimmune pathogenesis. Conversely, Clec4a4(−/−) mice exhibit resistance to microbial infection, accompanied by enhanced T-cell responses against microbes. Thus, our findings highlight roles of Clec4A4 in regulation of the function of CD8α(−) cDCs for control of the magnitude and quality of immune response.
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spelling pubmed-48320682016-04-25 Clec4A4 is a regulatory receptor for dendritic cells that impairs inflammation and T-cell immunity Uto, Tomofumi Fukaya, Tomohiro Takagi, Hideaki Arimura, Keiichi Nakamura, Takeshi Kojima, Naoya Malissen, Bernard Sato, Katsuaki Nat Commun Article Dendritic cells (DCs) comprise several subsets that are critically involved in the initiation and regulation of immunity. Clec4A4/DC immunoreceptor 2 (DCIR2) is a C-type lectin receptor (CLR) exclusively expressed on CD8α(−) conventional DCs (cDCs). However, how Clec4A4 controls immune responses through regulation of the function of CD8α(−) cDCs remains unclear. Here we show that Clec4A4 is a regulatory receptor for the activation of CD8α(−) cDCs that impairs inflammation and T-cell immunity. Clec4a4(−/−)CD8α(−) cDCs show enhanced cytokine production and T-cell priming following Toll-like receptor (TLR)-mediated activation. Furthermore, Clec4a4(−/−) mice exhibit TLR-mediated hyperinflammation. On antigenic immunization, Clec4a4(−/−) mice show not only augmented T-cell responses but also progressive autoimmune pathogenesis. Conversely, Clec4a4(−/−) mice exhibit resistance to microbial infection, accompanied by enhanced T-cell responses against microbes. Thus, our findings highlight roles of Clec4A4 in regulation of the function of CD8α(−) cDCs for control of the magnitude and quality of immune response. Nature Publishing Group 2016-04-12 /pmc/articles/PMC4832068/ /pubmed/27068492 http://dx.doi.org/10.1038/ncomms11273 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Uto, Tomofumi
Fukaya, Tomohiro
Takagi, Hideaki
Arimura, Keiichi
Nakamura, Takeshi
Kojima, Naoya
Malissen, Bernard
Sato, Katsuaki
Clec4A4 is a regulatory receptor for dendritic cells that impairs inflammation and T-cell immunity
title Clec4A4 is a regulatory receptor for dendritic cells that impairs inflammation and T-cell immunity
title_full Clec4A4 is a regulatory receptor for dendritic cells that impairs inflammation and T-cell immunity
title_fullStr Clec4A4 is a regulatory receptor for dendritic cells that impairs inflammation and T-cell immunity
title_full_unstemmed Clec4A4 is a regulatory receptor for dendritic cells that impairs inflammation and T-cell immunity
title_short Clec4A4 is a regulatory receptor for dendritic cells that impairs inflammation and T-cell immunity
title_sort clec4a4 is a regulatory receptor for dendritic cells that impairs inflammation and t-cell immunity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832068/
https://www.ncbi.nlm.nih.gov/pubmed/27068492
http://dx.doi.org/10.1038/ncomms11273
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