Association of periostin expression with eosinophilic inflammation in nasal polyps

Abstract

by GSK-3b leads to the instability of b-catenin, reducing translocation of b-catenin into the nucleus, which can be associated with tumorigenesis. In this study we established the critical link between GSK-3b and Foxp3 by means of tissue examination and in vitro analysis. Previously, Graham et al reported that GSK-3b inhibition is able to potentiate the suppressive activity of Treg cells, but whether other forms of posttranslational modifications, such as phosphorylation, can affect Foxp3 stability and Treg cell function has been largely unknown. In a recent study on rheumatoid arthritis, Nie et al investigated the relationship between Treg cells with pathogenic T cells at the site of chronic inflammation. They identified Ser 418 as a key phosphorylation site of Foxp3 that was responsible for the impaired Treg cell function in response to TNF-a. In this study we found a novel phosphorylation motif (Ser 270/274) of Foxp3, which can be recognized by proinflammatory GSK-3b. Interestingly, when we examined the p-Foxp3 protein using specific antibody against Ser 270 in NP tissues, we found p-Foxp3 (Ser 270) and showed a positive association of GSK-3b and p-Foxp3 (Ser 270) protein levels. Therefore these findings propose a molecular mechanism regulating inhibitory function of Treg cells, which might expand our knowledge on the pathogenesis of CRSwNP. Xingmei Wu, MD* Sihua Wang, PhD* Miaomiao Han, PhD* Bin Song, PhD Ping Ye, MD Shanshan Ma, MD Jun Li, MD Fenghong Chen, MD Geng Xu, PhD Qingqing Ding, PhD Jiahong Xia, PhD Huabin Li, PhD From the Allergy Center, Otorhinolaryngology Hospital, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; the Department of Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; the Allergy Division, Department of Otolaryngology, Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; the Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China; the Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; and the Department of Pathology, University of Missouri, Columbia, Mo. E-mail: qingqing_ding@ hotmail.com. Or: jiahong.xia@hust.edu.cn. Or: allergyli@163.com. *These authors contributed equally to this work. Supported by grants from the National Natural Science Foundations of China (nos. 81172512, 81271054, 81271056, and 81470673) and the Shanghai Committee of Science and Technology (no. 14DZ2260300). Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.