期刊
AIMS ALLERGY AND IMMUNOLOGY
卷 6, 期 3, 页码 188-199出版社
AMER INST MATHEMATICAL SCIENCES-AIMS
DOI: 10.3934/Allergy.2022014
关键词
IL-17; Th17; I?B-?; Regnase-1; mRNA stabilization; inflammation
类别
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- [20K07010]
- [19H03364]
Interleukin-17 (IL-17) is a proinflammatory cytokine that plays a crucial role in various inflammatory and autoimmune diseases. IL-17 has been found to regulate post-transcriptional modifications that affect the levels of inflammatory mRNA. Regnase-1 is an important regulator that downregulates IL-17-driven signaling pathways by degrading mRNA stability.
Interleukin (IL)-17 is a proinflammatory cytokine mainly produced by immune cells, especially activated T-helper 17 cells, which contribute to chronic inflammatory and autoimmune diseases including psoriasis. Although the molecular mechanisms of transcription in IL-17-mediated signaling pathways are well established, post-transcriptional control remains to be elucidated. Notably, IL-17 regulates post-transcriptional modifications, which induce elevated levels of target inflammatory mRNAs. Regnase-1, an endoribonuclease and deubiquitinase, post-transcriptionally downregulates various IL-17-driven signaling pathways, including mRNA stability. The ACT1-TBK1/IKK epsilon pathway and ARID5A were induced and activated by IL-17-stimulation, leading to the inhibition of inflammatory mRNA degradation by Regnase-1. In this review, we focus on IL-17-mediated mRNA stabilization of psoriasis-related I kappa B-zeta and provide novel therapeutic strategies for the treatment of Th17-mediated inflammation and autoimmunity.
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