PT  - JOURNAL ARTICLE
AU  - Shixiu Liang
AU  - Zicong Zhou
AU  - Zili Zhou
AU  - Jieyi Liu
AU  - Hangming Dong
AU  - Fei Zou
AU  - Haijin Zhao
AU  - Changhui Yu
AU  - Shaoxi Cai
TI  - CBX4 regulates long-form thymic stromal lymphopoietin-mediated airway inflammation through SUMOylation in HDM-induced asthma
AID  - 10.1101/2021.05.24.445396
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.05.24.445396
4099  - http://biorxiv.org/content/early/2021/05/26/2021.05.24.445396.short
4100  - http://biorxiv.org/content/early/2021/05/26/2021.05.24.445396.full
AB  - Rationale Thymic stromal lymphopoietin (TSLP) is present in two distinct isoforms, short-form (sfTSLP) and long-form (lfTSLP). lfTSLP promotes inflammation while sfTSLP inhibits inflammation in allergic asthma. However, little is known about the regulation of lfTSLP and sfTSLP during allergic attack in asthma airway epithelium.Methods and Results Here, we report that SUMOylation was enhanced in HDM-induced allergic asthma airway epithelium. Inhibition of SUMOylation significantly alleviated airway Th2 inflammation and lfTSLP expression. Mechanistically, CBX4, a SUMOylation E3 ligase, enhanced lfTSLP, but not sfTSLP, mRNA translation through the RNA binding protein, MEX-3B. MEX-3B promoted lfTSLP translation through binding of its KH domains to the lfTSLP mRNA. Furthermore, CBX4 regulated MEX-3B transcription in HBE through enhancing SUMOylation levels of the transcription factor, TFII-I.Conclusion We demonstrate an important mechanism whereby CBX4 promotes MEX-3B transcription through enhancing TFII-I SUMOylation, and MEX-3B enhances the expression of lfTSLP through binding to the lfTSLP mRNA and promoting its translation. Our findings uncover a novel target of CBX4 for therapeutic agents to lfTSLP-mediated asthma.Competing Interest StatementThe authors have declared no competing interest.CBX4chromobox 4HDMhouse dust mitelfTSLPlong-form thymic stromal lymphopoietinSUMO1Small Ubiquitin Like Modifier 1.