期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 110, 期 27, 页码 11097-11102出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1301257110
关键词
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资金
- National Key Basic Research Program of China [2013CB530500, 2013CB530603]
- National Natural Science Foundation of China [81230074, 81130084, 31070790, 31100635, 31270943]
Toll-like receptor (TLR) signaling is critical in innate response against invading pathogens. However, the molecular mechanisms for full activation of TLR-triggered innate immunity need to be fully elucidated. The broad complex tramtrack bric-a-brac/poxvirus and zinc finger (BTB/POZ) family is a class of transcription factors involved in many biological processes. However, few BTB/POZ proteins were reported to function in innate immune response. Zinc finger and BTB domain-containing 20 (ZBTB20), a member of BTB/POZ family, functions in neurogenesis and represses a-fetoprotein gene transcription in liver. However, the immunological functions of ZBTB20 remain unknown. Here, we found that myeloid cell-specific ZBTB20 KO mice were resistant to endotoxin shock and Escherichia coli-caused sepsis. ZBTB20 deficiency attenuated TLR-triggered production of proinflammatory cytokines and type I IFN in macrophages, which attributed to higher abundance of I kappa B alpha protein and impaired activity of NF-kappa B. Furthermore, ChIP and next generation high-throughput DNA sequencing assay showed that ZBTB20 specifically bound to I kappa B alpha gene promoter (+ 1 to + 60 region) after TLR activation. ZBTB20 could inhibit I kappa B alpha gene transcription, govern I kappa B alpha protein expression, and then promote NF-.B activation. Therefore, transcriptional repressor ZBTB20 is needed to promote full activation of TLR signaling and TLR-triggered innate immune response by selectively suppressing the suppressor I kappa B alpha gene transcription.
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