CLEC7A

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CLEC7A (C-type lectin domain family 7 member A, also known as dectin-1) is a pattern recognition receptor found on cells of the innate immune system, where it binds components of the cell wall of fungi and elicits an anti-fungal response. Injured mammalian cells may also release molecules that can act as ligands for pattern recognition receptors, called damage-associated molecular patterns, and several endogenous ligands for CLEC7A have been identified (Thiagarajan et al., 2013; Daley et al., 2017; Bode et al., 2019; Roesner et al., 2019).

CLEC7A is expressed by microglia and may have roles in development and response to damage of the central nervous system. In the developing mouse brain, CLEC7A-expressing microglia are located in regions undergoing neurogenesis and in white-matter tracts undergoing myelination, where these microglia appear to phagocytize dying oligodendrocytes (Li et al., 2019). In normal adult mice, CLEC7A-expressing microglia primarily are found in neurogenic areas (Li et al., 2019), with additional CLEC7A-expressing microglia appearing during aging (reviewed in Benmamar-Badel et al., 2020).

Clec7a expression is upregulated in microglia in several mouse models of neurodegenerative diseases (Keren-Shaul et al., 2017; Krasemann et al., 2017; Sala Frigerio et al., 2019; Hunter et al., 2021). Its expression also increases in response to traumatic brain injury (Castranio et al., 2017) and experimentally induced stroke (Ye et al., 2020; Zongyun et al., 2021) and during experimental autoimmune encephalitis (Deerhake et al., 2021). In mouse spinal cord, CLEC7A activation led to demyelination and axonal injury, while Clec7a knockout attenuated the retraction of corticospinal tract axons after a crush injury (Gensel et al., 2015).