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However, it is not clear whether and how Myo9b functions in malignant pleural effusion (MPE). In this study, our data showed that Myo9b expression levels correlated with lung cancer pleural metastasis, and nucleated cells in MPE from either patients or mice expressed a lower level of Myo9b than those in the corresponding blood. Myo9b deficiency in cancer cells suppressed MPE development via inhibition of migration. Myo9b deficiency in mice suppressed MPE development by decreasing TH1 cells and increasing TH17 cells. CD4+ naive T cells isolated from Myo9b\u2212\/\u2212 mouse spleens exhibited less TH1 cell differentiation and more TH17 cell differentiation in vitro. mRNA sequencing of nucleated cells showed that T cell\u2013specific adaptor protein (TSAd) was downregulated in Myo9b\u2212\/\u2212 mouse MPE, and enrichment of the H3K27me3 mark in the TSAd promoter region was found in the Myo9b\u2212\/\u2212 group. Naive T cells purified from wild type mouse spleens transfected with TSAd-specific small interfering RNAs (siRNAs) also showed less TH1 cell differentiation and more TH17 cell differentiation than those from the siRNA control group. Furthermore, downregulation of TSAd in mice using cholesterol-conjugated TSAd-specific siRNA suppressed MPE development, decreased TH1 cells, and increased TH17 cells in MPE in vivo. Taken together, Myo9b deficiency suppresses MPE development not only by suppressing pleural cancer metastasis but also by regulating TH1\/TH17 cell response via a TSAd-dependent pathway. This work suggests Myo9b and TSAd as novel candidates for future basic and clinical investigations of cancer.<\/jats:p>","DOI":"10.4049\/jimmunol.2000307","type":"journal-article","created":{"date-parts":[[2020,10,12]],"date-time":"2020-10-12T21:00:21Z","timestamp":1602536421000},"page":"2926-2935","source":"Crossref","is-referenced-by-count":14,"title":["TSAd Plays a Major Role in Myo9b-Mediated Suppression of Malignant Pleural Effusion by Regulating TH1\/TH17 Cell Response"],"prefix":"10.1093","volume":"205","author":[{"given":"Feng-Shuang","family":"Yi","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Capital Medical University , Beijing 100020 ,","place":["China"]},{"name":"Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University , Beijing 100020 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,","place":["China"]},{"name":"Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University , Beijing 100020 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3168-3548","authenticated-orcid":false,"given":"Xiu-Zhi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Capital Medical University , Beijing 100020 ,","place":["China"]},{"name":"Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University , Beijing 100020 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Ting","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Capital Medical University , Beijing 100020 ,","place":["China"]},{"name":"Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University , Beijing 100020 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Yu","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Capital Medical University , Beijing 100020 ,","place":["China"]},{"name":"Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University , Beijing 100020 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Bin","family":"Pei","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Capital Medical University , Beijing 100020 ,","place":["China"]},{"name":"Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University , Beijing 100020 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Feng","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Capital Medical University , Beijing 100020 ,","place":["China"]},{"name":"Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University , Beijing 100020 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Capital Medical University , Beijing 100020 ,","place":["China"]},{"name":"Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University , Beijing 100020 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Capital Medical University , Beijing 100020 ,","place":["China"]},{"name":"Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University , Beijing 100020 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Capital Medical University , Beijing 100020 ,","place":["China"]},{"name":"Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University , Beijing 100020 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