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\begin{document}

\title{CBX4 regulates long-form thymic stromal lymphopoietin-mediated airway
inflammation through SUMOylation in HDM-induced asthma mice}



\author[1]{changhui yu}%
\author[1]{shixiu liang}%
\author[1]{zicong zhou}%
\author[1]{zili zhou}%
\author[2]{Zhao Haijin}%
\author[3]{jieyi liu}%
\author[4]{Wufeng Huang}%
\author[5]{Hangming Dong}%
\author[6]{Fei Zou}%
\author[4]{Shaoxi Cai}%
\affil[1]{Nanfang Hospital, Southern Medical}%
\affil[2]{Nanfang hospital affilated to Southern Medical university}%
\affil[3]{Southern Medical University Nanfang Hospital}%
\affil[4]{Nanfang Hospital, Southern Medical University}%
\affil[5]{Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nan Fang Hospital, Southern Medical University, Guangzhou, 510515, China}%
\affil[6]{Southern Medical University}%


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  \date{June 16, 2024}


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\begin{abstract}
Abstract Background: 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.%
\end{abstract}%



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