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骨髓单核细胞和骨髓增生异常患者来源的树突状细胞具有功能异常,与对细菌感染的反应缺陷有关。

Bone Marrow Monocytes and Derived Dendritic Cells from Myelodysplastic Patients Have Functional Abnormalities Associated with Defective Response to Bacterial Infection.

机构信息

Clinical Pathology Laboratory, Hospital Israelita Albert Einstein, São Paulo 05652 000, Brazil; and.

Experimental Research Laboratory, Hospital Israelita Albert Einstein, São Paulo 05652 000, Brazil.

出版信息

J Immunol. 2020 Apr 15;204(8):2098-2109. doi: 10.4049/jimmunol.1900328. Epub 2020 Mar 16.

Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell diseases characterized by dysplasia of one or more hematologic lineages and a high risk of developing into acute myeloid leukemia. MDS patients have recurrent bacterial infections and abnormal expression of CD56 by monocytes. We investigated MDS patients' bone marrow CD56/CD56 monocytes and their in vitro-derived dendritic cell populations in comparison with cells obtained from disease-free subjects. We found that monocytes from MDS patients, irrespective of CD56 expression, have reduced phagocytosis activity and low expression of genes involved in triggering immune responses, regulation of immune and inflammatory response signaling pathways, and in the response to LPS. Dendritic cells derived in vitro from MDS monocytes failed to develop dendritic projections and had reduced expression of HLA-DR and CD86, suggesting that Ag processing and T cell activation capabilities are impaired. In conclusion, we identified, in both CD56 and CD56 monocytes from MDS patients, several abnormalities that may be related to the increased susceptibility to infections observed in these patients.

摘要

骨髓增生异常综合征(MDS)是一组异质性造血干细胞疾病,其特征为一个或多个血液系统谱系的发育不良和发展为急性髓系白血病的高风险。MDS 患者经常发生细菌感染,且单核细胞异常表达 CD56。我们研究了 MDS 患者骨髓 CD56/CD56 单核细胞及其体外衍生的树突状细胞群体,与无疾病患者获得的细胞进行比较。我们发现,MDS 患者的单核细胞,无论 CD56 表达如何,吞噬活性降低,参与触发免疫反应、调节免疫和炎症反应信号通路以及对 LPS 反应的基因表达降低。体外从 MDS 单核细胞衍生的树突状细胞未能发育出树突状突起,并且 HLA-DR 和 CD86 的表达降低,表明 Ag 处理和 T 细胞激活能力受损。总之,我们在 MDS 患者的 CD56 和 CD56 单核细胞中鉴定出几种异常,这些异常可能与这些患者观察到的易感染性增加有关。

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