LAUSR

Thymic stromal lymphopoietin (TSLP) presents 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. 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 mRNA translation, but not sfTSLP, through the RNA binding protein, MEX-3B. MEX-3B promoted lfTSLP translation by binding the lfTSLP mRNA through its KH domains. Furthermore, CBX4 regulated MEX-3B transcription in human bronchial epithelial cell (HBE) through enhancing SUMOylation levels of the transcription factor, TFII-I. In 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.