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您的检索式：作者名="Shaoqiu Leng"
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| 1 | Glucocorticoid receptor modulates myeloid-derived suppressor cell function via mitochondrial metabolism in immune thrombocytopenia显示文摘Myeloid-derived suppressor cells(MDSCs)are a heterogeneous population of immature cells and natural inhibitors of adaptive immunity.Intracellular metabolic changes in MDSCs exert a direct immunological influence on their suppressive activity.Our previous study demonstrated that high-dose dexamethasone(HD-DXM)corrected the functional impairment of MDSCs in immune thrombocytopenia(ITP);however,the MDSC population was not restored in nonresponders,and the mechanism remained unclear.In this study,altered mitochondrial physiology and reduced mitochondrial gene transcription were detected in MDSCs from HD-DXM nonresponders,accompanied by decreased levels of carnitine palmitoyltransferase-1(CPT-1),a rate-limiting enzyme in fatty acid oxidation(FAO).Blockade of FAO with a CPT-1 inhibitor abolished the immunosuppressive function of MDSCs in HD-DXM responders.We also report that MDSCs from ITP patients had lower expression of the glucocorticoid receptor(GR),which can translocate into mitochondria to regulate the transcription of mitochondrial DNA(mtDNA)as well as the level of oxidative phosphorylation.It was confirmed that the expression of CPT-1 and mtDNA-encoded genes was downregulated in GR-siRNA-treated murine MDSCs.Finally,by establishing murine models of active and passive ITP via adoptive transfer of DXM-modulated MDSCs,we confirmed that GR-silenced MDSCs failed to alleviate thrombocytopenia in mice with ITP.In conclusion,our study indicated that impaired aerobic metabolism in MDSCs participates in the pathogenesis of glucocorticoid resistance in ITP and that intact control of MDSC metabolism by GR contributes to the homeostatic regulation of immunosuppressive cell function. | Yu Hou Jie Xie Shuwen Wang Daqi Li Lingjun Wang Haoyi Wang Xiaofei Ni Shaoqiu Leng Guosheng Li Ming Hou Jun Peng | 2022 | Cellular & Molecular Immunology2022，19，7： | 4 |
| 2 | Deciphering transcriptome alterations in bone marrow hematopoiesis at single-cell resolution in immune thrombocytopenia显示文摘Immune thrombocytopenia(ITP)is an autoimmune disorder,in which megakaryocyte dysfunction caused by an autoimmune reaction can lead to thrombocytopenia,although the underlying mechanisms remain unclear.Here,we performed single-cell transcriptome profiling of bone marrow CD34+hematopoietic stem and progenitor cells(HSPCs)to determine defects in megakaryopoiesis in ITP.Gene expression,cell-cell interactions,and transcriptional regulatory networks varied in HSPCs of ITP,particularly in immune cell progenitors.Differentially expressed gene(DEG)analysis indicated that there was an impaired megakaryopoiesis of ITP.Flow cytometry confirmed that the number of CD9+and HES1+cells from Lin−CD34+CD45RA−HSPCs decreased in ITP.Liquid culture assays demonstrated that CD9+Lin−CD34+CD45RA−HSPCs tended to differentiate into megakaryocytes;however,this tendency was not observed in ITP patients and more erythrocytes were produced.The percentage of megakaryocytes differentiated from CD9+Lin−CD34+CD45RA−HSPCs was 3-fold higher than that of the CD9−counterparts from healthy controls(HCs),whereas,in ITP patients,the percentage decreased to only 1/4th of that in the HCs and was comparable to that from the CD9−HSPCs.Additionally,when co-cultured with pre-B cells from ITP patients,the differentiation of CD9+Lin−CD34+CD45RA−HSPCs toward the megakaryopoietic lineage was impaired.Further analysis revealed that megakaryocytic progenitors(MkP)can be divided into seven subclusters with different gene expression patterns and functions.The ITP-associated DEGs were MkP subtype-specific,with most DEGs concentrated in the subcluster possessing dual functions of immunomodulation and platelet generation.This study comprehensively dissects defective hematopoiesis and provides novel insights regarding the pathogenesis of ITP. | Yan Liu Xinyi Zuo Peng Chen Xiang Hu Zi Sheng Anli Liu Qiang Liu Shaoqiu Leng Xiaoyu Zhang Xin Li Limei Wang Qi Feng Chaoyang Li Ming Hou Chong Chu Shihui Ma Shuwen Wang Jun Peng | 2022 | Signal Transduction and Targeted Therapy2022，7，11： | 0 |
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