Innate immunity

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Autoimmune-associated clec16a Modulates Inflammasome Activity in Human Macrophages

Thursday, June 15
5:45 PM - 7:00 PM

C-type lectin domain family 16 member A (CLEC16A) is genetically-associated with a spectrum of autoimmune diseases including type I diabetes, multiple sclerosis and systemic lupus erythematosus (SLE). Functional characterization studies of Drosophila and mammalian CLEC16A homologues revealed their regulatory roles in different aspects of autophagy. Recent research advances in autophagy reveal its cross-regulatory relationship with inflammasome and have prompted us to evaluate the role of CLEC16A in inflammasome induction. The functional role of CLEC16A in inflammasome pathway was investigated using human monocyte-derived macrophages. Specific siRNAs targeting CLEC16A in macrophages resulted in a reduction in IL-1β secretion upon lipopolysaccharides stimulation with nigericin or poly(dA-dT), indicating that CLEC16 could modulate NLRP3 and AIM2 inflammasomes activity. Expression analyses showed that the inhibition of CLEC16A had minimal impact on mRNA levels of NLRP3, adaptor protein apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), interleukin-1 converting enzyme caspase-1 and the precursor pro-IL-1β, suggesting CLEC16A may act indirectly on the NLRP3 inflammasome pathway. Macrophages derived from SLE patients exhibited higher CLELC16A mRNA expression when compared with healthy controls. Interestingly, SLE macrophages produced more IL-1β upon NLRP3 as well as AIM2 inflammasomes activation. Taken together, CLEC16A may indirectly modulate inflammasome activity and affect IL-1β production in SLE macrophages. The mechanism involved is currently under further investigation.

Vera SAU FONG.. Chan

Assistant Professor
The University of Hong Kong

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    Michelle WM Li

    The University of Hong Kong

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      Chak Sing Lau

      The University of Hong Kong

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