C-type lectin domain family 4 member A

Definition:

C-type lectin receptor that binds carbohydrates mannose and fucose but also weakly interacts with N-acetylglucosamine (GlcNAc) in a Ca(2+)-dependent manner. Involved in regulating immune reactivity. Once triggered by antigen, it is internalized by clathrin-dependent endocytosis and delivers its antigenic cargo into the antigen presentation pathway resulting in cross-priming of CD8(+) T cells. This cross-presentation and cross-priming are enhanced by TLR7 and TLR8 agonists with increased expansion of the CD8(+) T cells, high production of IFNG and TNF with reduced levels of IL4, IL5 and IL13. In plasmacytoid dendritic cells, inhibits TLR9-mediated IFNA and TNF production. May be involved via its ITIM motif (immunoreceptor tyrosine-based inhibitory motifs) in the inhibition of B-cell-receptor-mediated calcium mobilization and protein tyrosine phosphorylation.; (Microbial infection) Involved in the interaction between HIV-1 virus and dendritic cells. Enhances HIV-1 binding/entry and virus infection. Requires ITIM motif-associated signal transduction pathway involving phosphatases PTPN6 and PTPN11, SYK, Src kinases and MAP kinases.

References:

[1]. Eynav Klechevsky, et al. Cross-priming CD8+ T cells by targeting antigens to human dendritic cells through DCIR. Blood. 2010 Sep 9;116(10):1685-97. [Content Brief]

[2]. Alexandra A Lambert, et al. DCIR-mediated enhancement of HIV-1 infection requires the ITIM-associated signal transduction pathway. Blood. 2011 Jun 16;117(24):6589-99. [Content Brief]

[3]. E E Bates, et al. APCs express DCIR, a novel C-type lectin surface receptor containing an immunoreceptor tyrosine-based inhibitory motif. J Immunol. 1999 Aug 15;163(4):1973-83. [Content Brief]

[4]. Masamichi Nagae, et al. Crystal structure of human dendritic cell inhibitory receptor C-type lectin domain reveals the binding mode with N-glycan. FEBS Lett. 2016 Apr;590(8):1280-8. [Content Brief]

[5]. Friederike Meyer-Wentrup, et al. Targeting DCIR on human plasmacytoid dendritic cells results in antigen presentation and inhibits IFN-alpha production. Blood. 2008 Apr 15;111(8):4245-53. [Content Brief]

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