CLEC7A


C-type lectin domain family 7 member A or Dectin-1 is a protein that in humans is encoded by the CLEC7A gene. CLEC7A is a member of the C-type lectin/C-type lectin-like domain superfamily. The encoded glycoprotein is a small type II membrane receptor with an extracellular C-type lectin-like domain fold and a cytoplasmic domain with a partial immunoreceptor tyrosine-based activation motif. It functions as a pattern-recognition receptor for a variety of β-1,3-linked and β-1,6-linked glucans from fungi and plants, and in this way plays a role in innate immune response. Expression is found on myeloid dendritic cells, monocytes, macrophages and B cells. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region.

Structure

Dectin-1 is a transmembrane protein containing an immunoreceptor tyrosine-based activation -like motif in its intracellular tail and one C-type lectin-like domain in the extracellular region. The CRD is separated from the membrane by a stalk region. CLEC7A contains putative N-linked sites of glycosylation in the stalk region.
CLEC7A is expressed by macrophages, neutrophils and dendritic cells. Expression has also been studied on other immune cells including eosinophils and B cells.

Function

The C-type lectin receptors are class of signalling pattern recognition receptors which are involved in antifungal immunity, but also play important roles in immune responses to other pathogens such as bacteria, viruses and nematodes. As a member of this receptor family, dectin-1 recognizes β-glucans and carbohydrates found in fungal cell walls, some bacteria and plants, but may also recognize other unidentified molecules. Ligand binding induces intracellular signalling via the ITAM-like motif. CLEC7A can induce both Syk dependent or Syk independent pathways. Dimerization of dectin-1 upon ligand binding leads to tyrosine phosphorylation by Src family kinases and recruitment of Syk. Syk activates transcription factor NFκB. This transcription factor is responsible for the production of numerous inflammatory cytokines and chemokines such as TNF, IL-23, IL-6, IL-2. Other responses include: respiratory burst, production of arachidonic acid metabolites, dendritic cell maturation, and phagocytosis of the ligand.

Antifungal immunity

CLEC7A has been shown to recognize species of several fungal genera, including Saccharomyces, Candida, Pneumocystis, Coccidioides, Penicillium and others. Recognition of these organisms triggers many protective pathways, such as fungal uptake by phagocytosis and killing via hypochlorite generation. Activation of dectin-1 also triggers expression of many protecting antifungal cytokines and chemokines and the development of Th17.
Histoplasma capsulatum can evade recognition of β-glucan via CLEC7A on phagocytic cells by secreting an enzyme that removes exposed β-glucans or by masking the β-glucan with α-glucan.

Co-stimulatory molecule

Also operating as a co-stimulatory molecule via recognition of an endogenous ligand on T-cells, which leads to cellular activation and proliferation, CLEC7A can bind both CD4+ and CD8+ T cells.