PMID- 27068492
OWN - NLM
STAT- MEDLINE
DCOM- 20160912
LR  - 20181113
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 7
DP  - 2016 Apr 12
TI  - Clec4A4 is a regulatory receptor for dendritic cells that impairs inflammation 
      and T-cell immunity.
PG  - 11273
LID - 10.1038/ncomms11273 [doi]
LID - 11273
AB  - 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 CD8alpha(-) conventional DCs 
      (cDCs). However, how Clec4A4 controls immune responses through regulation of the 
      function of CD8alpha(-) cDCs remains unclear. Here we show that Clec4A4 is a 
      regulatory receptor for the activation of CD8alpha(-) cDCs that impairs inflammation 
      and T-cell immunity. Clec4a4(-/-)CD8alpha(-) 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 CD8alpha(-) cDCs for control of the magnitude and 
      quality of immune response.
FAU - Uto, Tomofumi
AU  - Uto T
AD  - Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, 
      University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
FAU - Fukaya, Tomohiro
AU  - Fukaya T
AD  - Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, 
      University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
FAU - Takagi, Hideaki
AU  - Takagi H
AD  - Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, 
      University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
FAU - Arimura, Keiichi
AU  - Arimura K
AD  - Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, 
      University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
AD  - Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of 
      Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
FAU - Nakamura, Takeshi
AU  - Nakamura T
AD  - Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, 
      University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
AD  - Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine, 
      University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
FAU - Kojima, Naoya
AU  - Kojima N
AD  - Department of Applied Biochemistry, Tokai University, 4-1-1 Kita-kaname, 
      Hiratsuka-shi, 259-1292 Kanagawa, Japan.
FAU - Malissen, Bernard
AU  - Malissen B
AD  - Centre d'Immunologie de Marseille-Luminy, Universite de la Mediterrannee, Case 
      906, Institut National de la Sante et de la Recherche Medicale U631, and Centre 
      National de la Recherche Scientifique UMR6102, Marseille 13288, France.
FAU - Sato, Katsuaki
AU  - Sato K
AD  - Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, 
      University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
AD  - Japan Science and Technology Agency, Precursory Research for Embryonic Science 
      and Technology (PRESTO), 4-1-8 Hon-cho, Kawaguchi, Saitama 332-0012, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160412
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (CD8 Antigens)
RN  - 0 (Cytokines)
RN  - 0 (DCIR2 protein, mouse)
RN  - 0 (Epitopes)
RN  - 0 (Ligands)
RN  - 0 (Polysaccharides)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Animals
MH  - Bacterial Infections/immunology/prevention & control
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8 Antigens/metabolism
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cytokines/biosynthesis
MH  - Dendritic Cells/*immunology
MH  - Encephalomyelitis, Autoimmune, Experimental/immunology/pathology
MH  - Epitopes/immunology
MH  - Host-Pathogen Interactions/immunology
MH  - *Immunity, Cellular
MH  - Inflammation/*pathology
MH  - Ligands
MH  - Mice, Inbred C57BL
MH  - Polysaccharides/metabolism
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Receptors, Cell Surface/chemistry/*metabolism
MH  - Receptors, Immunologic/chemistry/*metabolism
MH  - Retroviridae/metabolism
MH  - T-Lymphocytes/*immunology
MH  - Toll-Like Receptors/metabolism
MH  - Transduction, Genetic
PMC - PMC4832068
EDAT- 2016/04/14 06:00
MHDA- 2016/09/13 06:00
PMCR- 2016/04/12
CRDT- 2016/04/13 06:00
PHST- 2015/10/01 00:00 [received]
PHST- 2016/03/08 00:00 [accepted]
PHST- 2016/04/13 06:00 [entrez]
PHST- 2016/04/14 06:00 [pubmed]
PHST- 2016/09/13 06:00 [medline]
PHST- 2016/04/12 00:00 [pmc-release]
AID - ncomms11273 [pii]
AID - 10.1038/ncomms11273 [doi]
PST - epublish
SO  - Nat Commun. 2016 Apr 12;7:11273. doi: 10.1038/ncomms11273.