| First Author | Uto T | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 11273 | PubMed ID | 27068492 |
| Mgi Jnum | J:236894 | Mgi Id | MGI:5810050 |
| Doi | 10.1038/ncomms11273 | Citation | Uto T, et al. (2016) Clec4A4 is a regulatory receptor for dendritic cells that impairs inflammation and T-cell immunity. Nat Commun 7:11273 |
| abstractText | 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. |
