Clec4A4 is a regulatory receptor for dendritic cells that impairs inflammation and T-cell immunity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27068492.
- Also identified by DOI 10.1038/ncomms11273 and PMC identifier 4832068.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Dendritic Cells
- Immunity, Cellular
- Inflammation
- Receptors, Cell Surface
- Receptors, Immunologic
- T-Lymphocytes