Disease relevance of Clec4n

• Using a soluble fusion protein of dectin-2 (sDec2) which should inhibit this interaction, we studied the effect on contact hypersensitivity (CHS) and its modulation by UV radiation [1].

High impact information on Clec4n

• It was postulated that dectin-2 interacts with its putative ligands on T cells and that the interaction may deliver costimulatory signals in naive T cells [1].
• Epidermal Langerhans cell-targeted gene expression by a dectin-2 promoter [2].
• Previously, we identified dectin-2, a C-type lectin receptor expressed selectively by LC-like XS cell lines and by LC within mouse epidermis [2].
• The expression pattern of this molecule, termed "dectin-2," was almost indistinguishable from that for dectin-1; that is, both were expressed abundantly at mRNA and protein levels by the XS52 DC line, but not by non-DC lines, and both were detected in spleen and thymus, as well as in skin resident DC (i.e. Langerhans cells) [3].
• We propose that dectin-2 and its isoforms, together with dectin-1, represent a unique subfamily of DC-associated C-type lectins [3].

Biological context of Clec4n

• Genomic analyses indicated that a full-length dectin-2 (alpha isoform) is encoded by 6 exons, whereas truncated isoforms (beta and gamma) are produced by alternative splicing [3].
• In ICR mice engineered to express the dectin-2 gene promoter linked to a luciferase reporter gene, we found broadband UV-B treatment in vivo to activate the promoter in LC [4].

Anatomical context of Clec4n

• Dectin-2 is predominantly myeloid restricted and exhibits unique activation-dependent expression on maturing inflammatory monocytes elicited in vivo [5].
• In naive mice, Dectin-2 has a novel distribution pattern compared with other myeloid markers, but is predominantly expressed by a wide variety of tissue macrophages [5].
• Ultraviolet-B radiation upregulates expression of dectin-2 on epidermal Langerhans cells by activating the gene promoter [4].
• The C-type lectin receptor, dectin-2, expressed preferentially by LC and dendritic cells, has also been shown to be involved in inducing this form of UV-B-induced immunosuppression [4].
• In cattle, dectin-2 expressed by dendritic cells may be clinically involved in the recognition of invading antigens in lymph nodes [6].

Analytical, diagnostic and therapeutic context of Clec4n

• Taken together, these data indicate that dectin-2 and its yet unidentified ligand may play a crucial role in the mediation of UV-induced immunosuppression [1].
• Interestingly, reverse transcriptase-polymerase chain reaction and immunoblotting revealed multiple bands of dectin-2 transcripts and proteins suggesting molecular heterogeneity [3].
• Our findings lay the foundation for use of the dectin-2 promoter in LC-targeted gene expression systems that may enhance vaccination efficacy and regulate immune responses [2].
• This change in Dectin-2 expression occurs on 'inflammatory' monocytes after arrival at the inflammatory lesion as demonstrated by adoptive cell-transfer studies, and is independent of whether the macrophages elicited by the stimuli ultimately expressed Dectin-2 [5].

References