CLEC9A Is a Novel Activation C-type Lectin-like Receptor Expressed on BDCA3+ Dendritic Cells and a Subset of Monocytes

TLDR

CLEC9A is a group V C‑type lectin‑like receptor encoded within the natural killer gene complex and part of the Dectin‑1 receptor cluster. The study reports the first characterization of CLEC9A. CLEC9A is expressed only on BDCA3⁺ dendritic cells and a small subset of CD14⁺CD16⁻ monocytes as a glycosylated surface dimer that mediates endocytosis but not phagocytosis, contains an ITAM‑like motif that recruits Syk kinase, induces pro‑inflammatory cytokine production, and functions as an activation receptor.

Abstract

We describe here the first characterization of CLEC9A, a group V C-type lectin-like receptor located in the "Dectin-1 cluster" of related receptors, which are encoded within the natural killer (NK)-gene complex. Expression of human CLEC9A is highly restricted in peripheral blood, being detected only on BDCA3(+) dendritic cells and on a small subset of CD14(+)CD16(-) monocytes. CLEC9A is expressed at the cell surface as a glycosylated dimer and can mediate endocytosis, but not phagocytosis. CLEC9A possesses a cytoplasmic immunoreceptor tyrosine-based activation-like motif that can recruit Syk kinase, and we demonstrate, using receptor chimeras, that this receptor can induce proinflammatory cytokine production. These data indicate that CLEC9A functions as an activation receptor.