Background and aims C-type lectin domain family 16 member A (CLEC16A) has been associated with autoimmune diseases such as systemic lupus erythematosus, multiple sclerosis and type I diabetes in various genome-wide association studies. Subsequent studies revealed that mouse/human CLEC16A and its Drosophila homolog endosomal maturation defective isoform A (EMA) are involved in different aspects of autophagy, the regulated degradation of cellular components that are in excess or dysfunctional. Crosstalk between autophagy and inflammasome activity of innate immune responses has been reported and inflammasomes are activated in various autoimmune diseases. We thus sought to investigate the role of CLEC16A in inflammasome pathway in this study.
Methods Functional genetic studies of CLEC16A in NLRP3 and AIM2 inflammasome pathways using monocyte-derived macrophages isolated from peripheral blood mononuclear cells of healthy individuals were performed.
Results During induction of NLRP3 inflammasome pathway by nigericin, a knockdown of CLEC16A using specific siRNAs inhibited secretion of interleukin-1β (IL-1β), an inflammasome pathway effector. Its secretion during AIM2 inflammasome induction by intracellular dsDNA poly(dA:dT) however was not affected in the siCLEC16A group. The induction of NLRP3 mRNA level upon lipopolysaccharide stimulation was suppressed in the siCLEC16A group. No significant changes in mRNA levels was observed in other selected genes of NLRP3 inflammasome pathway, namely the adaptor protein ASC, interleukin-1 converting enzyme caspase-1 and precursor pro-IL-1β.
Conclusions These data suggest that CLEC16A regulates NLRP3 but not AIM2 inflammasome pathway and affects IL-1β secretion in part via NLRP3 level. The mechanism involved and its association with autoimmune diseases such as systemic lupus erythematosus remains to be elucidated.
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