医学
恶性胸腔积液
免疫学
T细胞
RAR相关孤儿受体γ
白细胞介素17
FOXP3型
CD8型
细胞因子
细胞凋亡
关贸总协定3
细胞毒性T细胞
炎症
生物
免疫系统
白细胞介素2受体
作者
Feng-Shuang Yi,Xin Zhang,Kan Zhai,Zhong‐Yin Huang,Xiu-Zhi Wu,Min-Ting Wu,Xin-Yu Shi,Xue-Bin Pei,Shu-Feng Dong,Wen Wang,Yuan Yang,Juan Du,Zeng-Tao Luo,Huan-Zhong Shi
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2020-10-12
卷期号:205 (10): 2926-2935
标识
DOI:10.4049/jimmunol.2000307
摘要
Emerging evidence indicates that Myo9b is a cancer metastasis-related protein and functions in a variety of immune-related diseases. 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-/- mouse spleens exhibited less TH1 cell differentiation and more TH17 cell differentiation in vitro. mRNA sequencing of nucleated cells showed that T cell-specific adaptor protein (TSAd) was downregulated in Myo9b-/- mouse MPE, and enrichment of the H3K27me3 mark in the TSAd promoter region was found in the Myo9b-/- 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.
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