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Nat Commun. 2016 Apr 12;7:11273. doi: 10.1038/ncomms11273.

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

Author information

1
Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
2
Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
3
Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
4
Department of Applied Biochemistry, Tokai University, 4-1-1 Kita-kaname, Hiratsuka-shi, 259-1292 Kanagawa, Japan.
5
Centre d'Immunologie de Marseille-Luminy, Université de la Méditerrannée, Case 906, Institut National de la Santé et de la Recherche Médicale U631, and Centre National de la Recherche Scientifique UMR6102, Marseille 13288, France.
6
Japan Science and Technology Agency, Precursory Research for Embryonic Science and Technology (PRESTO), 4-1-8 Hon-cho, Kawaguchi, Saitama 332-0012, Japan.

Abstract

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.

PMID:
27068492
PMCID:
PMC4832068
DOI:
10.1038/ncomms11273
[Indexed for MEDLINE]
Free PMC Article

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