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您的检索式：作者名="Wanwei Sun"
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| 1 | DOCK2 regulates antifungal immunity by regulating RAC GTPase activity显示文摘Fungal infections cause~1.5 million deaths each year worldwide,and the mortality rate of disseminated candidiasis currently exceeds that of breast cancer and malaria.The major reasons for the high mortality of candidiasis are the limited number of antifungal drugs and the emergence of drug-resistant species.Therefore,a better understanding of antifungal host defense mechanisms is crucial for the development of effective preventive and therapeutic strategies.Here,we report that DOCK2(dedicator of cytokinesis 2)promotes indispensable antifungal innate immune signaling and proinflammatory gene expression in macrophages.DOCK2-deficient macrophages exhibit decreased RAC GTPase(Rac family small GTPase)activation and ROS(reactive oxygen species)production,which in turn attenuates the killing of intracellular fungi and the activation of downstream signaling pathways.Mechanistically,after fungal stimulation,activated SYK(spleen-associated tyrosine kinase)phosphorylates DOCK2 at tyrosine 985 and 1405,which promotes the recruitment and activation of RAC GTPases and then increases ROS production and downstream signaling activation.Importantly,nanoparticle-mediated delivery of in vitro transcribed(IVT)Rac1 mRNA promotes the activity of Rac1 and helps to eliminate fungal infection in vivo.Taken together,this study not only identifies a critical role of DOCK2 in antifungal immunity via regulation of RAC GTPase activity but also provides proof of concept for the treatment of invasive fungal infections by using IVT mRNA. | Xiaojian Ma Xi Tan Bingbing Yu Wanwei Sun Heping Wang Huijun Hu Yanyun Du Ruirui He Ru Gao Qianwen Peng Zhihui Cui Ting Pan Xiong Feng Junhan Wang Chengqi Xu Bin Zhu Wei Liu Chenhui Wang | 2022 | Cellular & Molecular Immunology2022，19，5： | 1 |
| 2 | TRIM34 attenuates colon inflammation and tumorigenesis by sustaining barrier integrity显示文摘Loss of the colonic inner mucus layer leads to spontaneously severe colitis and colorectal cancer.However,key host factors that may control the generation of the inner mucus layer are rarely reported.Here,we identify a novel function of TRIM34 in goblet cells(GCs)in controlling inner mucus layer generation.Upon DSS treatment,TRIM34 deficiency led to a reduction in Muc2 secretion by GCs and subsequent defects in the inner mucus layer.This outcome rendered TRIM34-deficient mice more susceptible to DSS-induced colitis and colitis-associated colorectal cancer.Mechanistic experiments demonstrated that TRIM34 controlled TLR signaling-induced Nox/Duox-dependent ROS synthesis,thereby promoting the compound exocytosis of Muc2 by colonic GCs that were exposed to bacterial TLR ligands.Clinical analysis revealed that TRIM34 levels in patient samples were correlated with the outcome of ulcerative colitis(UC)and the prognosis of rectal adenocarcinoma.This study indicates that TRIM34 expression in GCs plays an essential role in generating the inner mucus layer and preventing excessive colon inflammation and tumorigenesis. | Qiaoshi Lian Shanshan Yan Qi Yin Chenghua Yan Wanwei Zheng Wangpeng Gu Xinhao Zhao Weiguo Fan Xuezhen Li Liyan Ma Zhiyang Ling Yaguang Zhang Jie Liu Jinsong Li Bing Sun | 2021 | Cellular & Molecular Immunology2021，18，2： | 0 |
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