| 1 | Mycobacterium tuberculosis Mce2E suppresses the macrophage innate immune response and promotes epithelial cell proliferation显示文摘The intracellular pathogen Mycobacterium tuberculosis(Mtb)can survive in the host and cause disease by interfering with a variety of cellular functions.The mammalian cell entry 2(mce2)operon of Mtb has been shown to contribute to tuberculosis pathogenicity.However,little is known about the regulatory roles of Mtb Mce2 family proteins towards host cellular functions.Here we show that the Mce2 family protein Mce2E suppressed the macrophage innate immune response and promoted epithelial cell proliferation.Mce2E inhibited activation of the extracellular signal-regulated kinase(ERK)and Jun N-terminal kinase(JNK)mitogen-activated protein kinase(MAPK)signaling pathways in a non-canonical D motif(a MAPK-docking motif)-dependent manner,leading to reduced expression of TNF and IL-6 in macrophages.Furthermore,Mce2E promoted proliferation of human lung epithelium-derived lung adenoma A549 cells by inhibiting K48-linked polyubiquitination of eEF1A1 in aβstrand region-dependent manner.In summary,Mce2E is a novel multifunctional Mtb virulence factor that regulates host cellular functions in a niche-dependent manner.Our data suggest a potential novel target for TB therapy. | Lihua Qiang Jing Wang Yong Zhang Pupu Ge Qiyao Chai Bingxi Li Yi Shi Lingqiang Zhang George Fu Gao Cui Hua Liu | 2019 | Cellular & Molecular Immunology2019，16，4： | 7 |
| 2 | TRIM27 maintains gut homeostasis by promoting intestinal stem cell self-renewal显示文摘Dysregulation of gut homeostasis is associated with irritable bowel syndrome(IBS),a chronic functional gastrointestinal disorder affecting approximately 11.2%of the global population.The poorly understood pathogenesis of IBS has impeded its treatment.Here,we report that the E3 ubiquitin ligase tripartite motif-containing 27(TRIM27)is weakly expressed in IBS but highly expressed in inflammatory bowel disease(IBD),a frequent chronic organic gastrointestinal disorder.Accordingly,knockout of Trim27 in mice causes spontaneously occurring IBS-like symptoms,including increased visceral hyperalgesia and abnormal stool features,as observed in IBS patients.Mechanistically,TRIM27 stabilizesβ-catenin and thus activates Wnt/β-catenin signaling to promote intestinal stem cell(ISC)self-renewal.Consistent with these findings,Trim27 deficiency disrupts organoid formation,which is rescued by reintroducing TRIM27 orβ-catenin.Furthermore,Wnt/β-catenin signaling activator treatment ameliorates IBS symptoms by promoting ISC self-renewal.Taken together,these data indicate that TRIM27 is critical for maintaining gut homeostasis,suggesting that targeting the TRIM27/Wnt/β-catenin axis could be a potential treatment strategy for IBS.Our study also indicates that TRIM27 might serve as a potential biomarker for differentiating IBS from IBD. | Jing Wang Dongdong Zhao Zehui Lei Pupu Ge Zhe Lu Qiyao Chai Yong Zhang Lihua Qiang Yang Yu Xinwen Zhang Bingxi Li Shu Zhu Lingqiang Zhang Cui Hua Liu | 2023 | Cellular & Molecular Immunology2023，20，2： | 2 |
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