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Conference Paper: A novel transcript isoform of IFI16 attenuates inflammasome activation mediated by the cytosolic DNA sensor AIM2
Title | A novel transcript isoform of IFI16 attenuates inflammasome activation mediated by the cytosolic DNA sensor AIM2 |
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Authors | |
Issue Date | 2016 |
Citation | The 2016 Annual General Meeting and Scientific Meeting of the Hong Kong Society for Immunology (HKSI 2016), Hong Kong, 2016. How to Cite? |
Abstract | Upon sensing cytoplasmic dsDNA, AIM2 triggers the formation of a multiprotein complex called the inflammasome which drives proteolytic maturation of the proinflammatory cytokines, representing a critical component in host defense against pathogens. Excessive or persistent activation of AIM2 inflammasome is supposed to cause autoimmune and autoinflammatory diseases. In mice, p202, a naturally occurring dominant-negative antagonists of AIM2, acts as a brake of inflammasome-mediated inflammatory responses. However, this strategy has so far not been discovered in human since no human homolog of p202 was found. Here, we report a novel transcript isoform of human IFI16, which has a similar domain organization as mice p202. We named it as IFI16 and the original version became IFI16. Like p202, IFI16 contains two HIN domains, but lacks the pyrin domain. IFI16 is widely distributed in various human tissues and cell lines. IFI16 co-localizes with AIM2 in the cytoplasm, whereas IFI16 is predominantly restricted to the nucleus. IFI16 interacts with AIM2 and prevents ASC recruitment. IFI16 sequesters cytoplasmic dsDNA and render it unavailable for AIM2 sensing. Enforced expression of IFI16 inhibits AIM2 inflammasome activation, whereas knockdown of IFI16 augments IL-1 secretion triggered by dsDNA but not dsRNA. We therefore identified IFI16 as a functional equivalent of mice p202 that possess inhibitory effect on AIM2 inflammasome activation in the cytoplasm. |
Persistent Identifier | http://hdl.handle.net/10722/234410 |
DC Field | Value | Language |
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dc.contributor.author | Wang, F | - |
dc.contributor.author | Jin, D | - |
dc.date.accessioned | 2016-10-14T13:46:41Z | - |
dc.date.available | 2016-10-14T13:46:41Z | - |
dc.date.issued | 2016 | - |
dc.identifier.citation | The 2016 Annual General Meeting and Scientific Meeting of the Hong Kong Society for Immunology (HKSI 2016), Hong Kong, 2016. | - |
dc.identifier.uri | http://hdl.handle.net/10722/234410 | - |
dc.description.abstract | Upon sensing cytoplasmic dsDNA, AIM2 triggers the formation of a multiprotein complex called the inflammasome which drives proteolytic maturation of the proinflammatory cytokines, representing a critical component in host defense against pathogens. Excessive or persistent activation of AIM2 inflammasome is supposed to cause autoimmune and autoinflammatory diseases. In mice, p202, a naturally occurring dominant-negative antagonists of AIM2, acts as a brake of inflammasome-mediated inflammatory responses. However, this strategy has so far not been discovered in human since no human homolog of p202 was found. Here, we report a novel transcript isoform of human IFI16, which has a similar domain organization as mice p202. We named it as IFI16 and the original version became IFI16. Like p202, IFI16 contains two HIN domains, but lacks the pyrin domain. IFI16 is widely distributed in various human tissues and cell lines. IFI16 co-localizes with AIM2 in the cytoplasm, whereas IFI16 is predominantly restricted to the nucleus. IFI16 interacts with AIM2 and prevents ASC recruitment. IFI16 sequesters cytoplasmic dsDNA and render it unavailable for AIM2 sensing. Enforced expression of IFI16 inhibits AIM2 inflammasome activation, whereas knockdown of IFI16 augments IL-1 secretion triggered by dsDNA but not dsRNA. We therefore identified IFI16 as a functional equivalent of mice p202 that possess inhibitory effect on AIM2 inflammasome activation in the cytoplasm. | - |
dc.language | eng | - |
dc.relation.ispartof | AGM & Scientific Meeting of the Hong Kong Society for Immunology, HKSI 2016 | - |
dc.title | A novel transcript isoform of IFI16 attenuates inflammasome activation mediated by the cytosolic DNA sensor AIM2 | - |
dc.type | Conference_Paper | - |
dc.identifier.email | Wang, F: wangph@hku.hk | - |
dc.identifier.email | Jin, D: dyjin@hku.hk | - |
dc.identifier.authority | Jin, D=rp00452 | - |
dc.identifier.hkuros | 268395 | - |