CXXC5 promotes IRF7 de-methylation and promotes pDC antiviral immune response mechanisms.

On May 1st, the international journal The Journal of Experimental Medicine published online the latest findings of the Xiao Wei Research Group of the Pasteur Institute in Shanghai, Chinese Academy of Sciences: Epigenetic regulator CXXC5 recruits DNA demethylase Tet2 to regulate TLR 7/9-elicited IFN response in pDCs ("The oscic genetic molecule CXXC5 regulates TLR7/9-induced type I interferon expression in pDC by recruiting DNA demethylase Tet2").
The study found for the first time that the oscic genetic molecule CXXC5, specifically expressed in pulp-like dendrine cells (pDC), effectively removes viral infections by recruiting DNA demethylase enzyme Tet2, resulting in a low methylation state on CpG Island in the Irf7 gene promoter region.
This study is the first to discover the key role of the ode to genetic regulation mechanisms, especially DNA methylation modification, in regulating pDC function, to verify the important role of ode genetic mechanisms in immune cell development, differentiation and functional maintenance, and to provide new ideas for the treatment of bacterial infections and autoimmune diseases.
in the early stages of viral infection, pDC can rapidly produce a large number of type I interferons, so it plays an important role in controlling viral infection and regulating natural immune and adaptive immune responses.
So far, although the signal transducting pathway for pDC to activate transcription factor IRF7 through TLR7/9 signal, inducing type I interferon expression, is not clear as to why only pDC specifically expresses IRF7 in many immune cells.
Shanghai Pasteur Institute and Suzhou University jointly trained doctoral candidate Ma Shixin, under the guidance of researcher Xiao Wei and professor Gao Xiaoming, through screening found that the surface genetic molecule of the ZF-CXXC family CXXC5 specifically high expression in the pDC, and participated in the regulation of TLR7/9 and virus-induced type I interferon expression.
In terms of mechanism, it was found that CXXC5 binds to CpG Island in the Ilf7 gene promoter region through its CXXC domain, and then recruits DNA demethylase Tet2 to reduce the region's 5'-cytosine methylation level (5'-mC);
In RNA and DNA virus infection, the mice knocked out by the CXXC5 gene were unable to produce a large number of type I interferons quickly, thus losing the ability to resist viral infection, indicating that the surface genetic regulation mechanism mediated by CXXC5 plays an important role in host defense.
: CXXC5 promotes IRF7 de-methylation and promotes pDC antiviral immune response mechanisms.
, CXXC5 promotes CpG island de-methylation in the IRF7 starter region.
b, CXXC5 as an obituary genetic molecule regulates the expression of transcription factors such as IRF7 in pDC to promote its working pattern map of antiviral infection and immune response.
the study was supported by key projects of the National Natural Science Foundation of China, key research and development plans of the Ministry of Science and Technology and the "973" plan, and special category B of strategic pilot science and technology of the Chinese Academy of Sciences.
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