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

• Published in: Nature communications 2016-04, Vol.7 (1), p.11273-11273, Article 11273
• Main Authors: Uto, Tomofumi, Fukaya, Tomohiro, Takagi, Hideaki, Arimura, Keiichi, Nakamura, Takeshi, Kojima, Naoya, Malissen, Bernard, Sato, Katsuaki
• Format: Article
• Language: English
• Subjects: 13/1; 13/31; 13/44; 13/51; 13/95; 38/70; 631/250/1933; 631/250/2504/133; 631/250/256; 631/45/612/1237; Animals; Bacterial Infections - immunology; Bacterial Infections - prevention & control; CD4-Positive T-Lymphocytes - immunology; CD8 Antigens - metabolism; CD8-Positive T-Lymphocytes - immunology; Cytokines; Cytokines - biosynthesis; Dendritic cells; Dendritic Cells - immunology; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - pathology; Epitopes - immunology; Host-Pathogen Interactions - immunology; Humanities and Social Sciences; Immunity, Cellular; Immunology; Inflammation - pathology; Kinases; Life Sciences; Ligands; Mice, Inbred C57BL; multidisciplinary; Pathogens; Polysaccharides - metabolism; Protein Binding; Protein Structure, Tertiary; Receptors, Cell Surface - chemistry; Receptors, Cell Surface - metabolism; Receptors, Immunologic - chemistry; Receptors, Immunologic - metabolism; Regulation; Retroviridae - metabolism; Science; Science (multidisciplinary); T-Lymphocytes - immunology; Toll-Like Receptors - metabolism; Transduction, Genetic; Tumor necrosis factor-TNF
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms11273

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. Clec4A4 is a C-type lectin receptor highly expressed by CD8α − dendritic cells. Here the authors show that its loss of function results in enhanced T cell responses and exacerbated autoimmunity, implicating Clec4A4 in limiting activation of the CD8α − dendritic cells.