期刊
NATURE COMMUNICATIONS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms11273
关键词
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资金
- Ministry of Education, Science and Culture of Japan
- Japan Science and Technology Agency
- Precursory Research for Embryonic Science and Technology (PRESTO)
- Uehara Memorial Foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Takeda Science Foundation
- Kato Memorial Bioscience Foundation
- NOVARTIS Foundation (Japan) for the Promotion of Science
- Nagao Memorial Fund
- Grants-in-Aid for Scientific Research [25293117, 26860337] Funding Source: KAKEN
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 CD8 alpha(-) conventional DCs (cDCs). However, how Clec4A4 controls immune responses through regulation of the function of CD8 alpha(-) cDCs remains unclear. Here we show that Clec4A4 is a regulatory receptor for the activation of CD8 alpha(-) cDCs that impairs inflammation and T-cell immunity. Clec4a4(-/-) CD8 alpha(-) 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 CD8 alpha(-) cDCs for control of the magnitude and quality of immune response.
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