Dectin-2

Dectin2α or Dectin2, also known as CLEC6A, CLECSF10, and NKCL, belongs to the Ctype lectin family of transmembrane immune regulatory glycoproteins. Dectin 2α, CLEC4A/DCIR, CLEC4B/DCAR, CLEC4C/DLEC, CLEC4D/MCL, and CLEC4E/mincle constitute a subgroup of these molecules that exhibit approximately 40% amino acid (aa) sequence identity in their extracellular domains (ECD) and have a conserved cysteine spacing in their carbohydrate recognition domains (CRD). Mature mouse Dectin2α consists of a short cytoplasmic tail, a transmembrane segment, and an ECD with a stalk region and one CRD. Alternate splicing leads to partial deletion of the transmembrane segment and stalk ( β isoform) or a portion of the CRD (γ isoform). The full length Dectin2α isoform is a 27 kDa molecule that is primarily expressed on the surface of tissue macrophages and their precursors. The CRD of Dectin2α contains an EPN motif which is characteristic of calciumdependent mannosebinding lectins. Dectin2α selectively interacts with high mannose structures in the Man9GlcNAc2 configuration. It mediates the recognition of a variety of microorganisms, particularly the filamentous forms of yeast and fungii. The short cytoplasmic tail does not contain signaling motifs but mediates association with the ITAMcontaining Fc receptor γ subunit in macrophages. Ligation of Dectin2α induces tyrosine phosphorylation of the γ subunit, activation of NFκB, and enhanced release of TNFα and IL1ra. Macrophage Dectin2α is upregulated in vivo by inflammatory stimuli and UVB irradiation. It mediates the breaking of UVinduced tolerance by interacting with CD4+CD25+ regulatory T cells which then induce dendritic cells to release IL4, IL10, and TGFβ. Within the ECD, mouse Dectin2α shares 71% aa sequence identity with human and bovine Dectin2.