CLEC7A

C-type lectin domain family 7 member A or Dectin-1 is a is_associated_with::protein that in humans is encoded by the CLEC7A is_associated_with::gene. CLEC7A is a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) 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 is_associated_with::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 is_associated_with::glucans from fungi and plants, and in this way plays a role in innate immune response. Expression is found on myeloid is_associated_with::dendritic cells, is_associated_with::monocytes, is_associated_with::macrophages and is_associated_with::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 (ITAM)-like motif in its intracellular tail (which is involved in cellular activation) and one C-type lectin-like domain (carbohydrate-recognition domain, CRD) in the extracellular region (which recognizes β-glucans and endogenous ligands on T cells). 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 is_associated_with::macrophages, is_associated_with::neutrophils and is_associated_with::dendritic cells. Expression has also been studied on other immune cells including is_associated_with::eosinophils and is_associated_with::B cells.

Function
The is_associated_with::C-type lectin receptors are class of signalling is_associated_with::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 (endogenous ligand on is_associated_with::T-cells and ligand on is_associated_with::mycobacteria). 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 is_associated_with::Src family kinases and recruitment of is_associated_with::Syk. Syk activates transcription factor is_associated_with::NFκB. This transcription factor is responsible for the production of numerous inflammatory is_associated_with::cytokines and is_associated_with::chemokines such as is_associated_with::TNF, IL-23, IL-6, IL-2. Other responses include: is_associated_with::respiratory burst, production of is_associated_with::arachidonic acid metabolites, is_associated_with::dendritic cell maturation, and is_associated_with::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 respiratory burst. Activation of dectin-1 also triggers expression of many protecting antifungal cytokines and chemokines (TNF, CXCL2, IL-1b, IL-1a, CCL3, GM-CSF, G-CSF and IL-6) and the development of is_associated_with::Th17.

Co-stimulatory molecule
Dectin-1 can also operate 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.