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

Tomofumi Uto (1) , Tomohiro Fukaya (1) , Hideaki Takagi (1) , Keiichi Arimura (1) , Takeshi Nakamura (1) , Naoya Kojima (2) , Bernard Malissen (3) , Katsuaki Sato (1)

1 University of Miyazaki
2 Tokai University
3 CIML - Centre d'Immunologie de Marseille - Luminy

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.

Mots clés: Cell death and immune response; Dendritic cells; Inflammation; Membrane proteins

Domaines: Immunologie

Tomofumi Uto, Tomohiro Fukaya, Hideaki Takagi, Keiichi Arimura, Takeshi Nakamura, et al.. Clec4A4 is a regulatory receptor for dendritic cells that impairs inflammation and T-cell immunity. Nature Communications, 2016, 7, ⟨10.1038/ncomms11273⟩. ⟨hal-01438515⟩