气候变化领域集成服务门户(CCPortal): Induction of myelodysplasia by myeloid-derived suppressor cells

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DOI	10.1172/JCI67580
	Induction of myelodysplasia by myeloid-derived suppressor cells
	Chen, Xianghong; Eksioglu, Erika A.; Zhou, Junmin; Zhang, Ling; Djeu, Julie; Fortenbery, Nicole; Epling-Burnette, Pearlie; Van Bijnen, Sandra; Dolstra, Harry; Cannon, John; Youn, Je-in; Donatelli, Sarah S.; Qin, Dahui; De Witte, Theo; Tao, Jianguo; Wang, Huaquan; Cheng, Pingyan; Gabrilovich, Dmitry I.; List, Alan; Wei, Sheng
发表日期	2013
ISSN	0021-9738
起始页码	4595
结束页码	4611
卷号	123 期号:11
英文摘要	Myelodysplastic syndromes (MDS) are age-dependent stem cell malignancies that share biological features of activated adaptive immune response and ineffective hematopoiesis. Here we report that myeloid-derived suppressor cells (MDSC), which are classically linked to immunosuppression, inflammation, and cancer, were markedly expanded in the bone marrow of MDS patients and played a pathogenetic role in the development of ineffective hematopoiesis. These clonally distinct MDSC overproduce hematopoietic suppressive cytokines and function as potent apoptotic effectors targeting autologous hematopoietic progenitors. Using multiple transfected cell models, we found that MDSC expansion is driven by the interaction of the proinflammatory molecule S100A9 with CD33. These 2 proteins formed a functional ligand/receptor pair that recruited components to CD33's inununoreceptor tyrosine-based inhibition motif (ITIM), inducing secretion of the suppressive cytokines IL-10 and TGF-beta by immature myeloid cells. S100A9 transgenic mice displayed bone marrow accumulation of MDSC accompanied by development of progressive multilineage cytopenias and cytological dysplasia. Importantly, early forced maturation of MDSC by either all-trans-retinoic acid treatment or active imrnunoreceptor tyrosine-based activation motif-bearing (ITAM-bearing) adapter protein (DAP12) interruption of CD33 signaling rescued the hematologic phenotype. These findings indicate that primary bone marrow expansion of MDSC driven by the S100A9/CD33 pathway perturbs hematopoiesis and contributes to the development of MDS.
WOS研究方向	Research & Experimental Medicine
WOS类目	Medicine, Research & Experimental
来源期刊	JOURNAL OF CLINICAL INVESTIGATION
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/158609
作者单位	Wei, S (corresponding author), H Lee Moffitt Canc Ctr & Res Inst, MRC 4072,12902 Magnolia Dr, Tampa, FL 33647 USA.
推荐引用方式 GB/T 7714	Chen, Xianghong,Eksioglu, Erika A.,Zhou, Junmin,et al. Induction of myelodysplasia by myeloid-derived suppressor cells[J],2013,123(11).
APA	Chen, Xianghong.,Eksioglu, Erika A..,Zhou, Junmin.,Zhang, Ling.,Djeu, Julie.,...&Wei, Sheng.(2013).Induction of myelodysplasia by myeloid-derived suppressor cells.JOURNAL OF CLINICAL INVESTIGATION,123(11).
MLA	Chen, Xianghong,et al."Induction of myelodysplasia by myeloid-derived suppressor cells".JOURNAL OF CLINICAL INVESTIGATION 123.11(2013).