RT Journal Article
SR Electronic
T1 CBX4 regulates long-form thymic stromal lymphopoietin-mediated airway inflammation through SUMOylation in HDM-induced asthma
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.05.24.445396
DO 10.1101/2021.05.24.445396
A1 Shixiu Liang
A1 Zicong Zhou
A1 Zili Zhou
A1 Jieyi Liu
A1 Hangming Dong
A1 Fei Zou
A1 Haijin Zhao
A1 Changhui Yu
A1 Shaoxi Cai
YR 2021
UL http://biorxiv.org/content/early/2021/05/26/2021.05.24.445396.abstract
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.