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人类炎症性单核细胞衍生树突状细胞的广泛表型。

Extensive Phenotype of Human Inflammatory Monocyte-Derived Dendritic Cells.

机构信息

Immunogenomics and Inflammation Research Team, University of Lyon, Edouard Herriot Hospital, 69437 Lyon, France.

Immunology Department, Lyon-Sud Hospital, Hospices Civils de Lyon, 69310 Pierre-Bénite, France.

出版信息

Cells. 2021 Jul 2;10(7):1663. doi: 10.3390/cells10071663.

Abstract

Inflammatory monocyte-derived dendritic cells (Mo-DCs) have been described in several chronic inflammatory disorders, such as rheumatoid arthritis (RA), and are suspected to play a detrimental role by fueling inflammation and skewing adaptive immune responses. However, the characterization of their phenotype is still limited, as well as the comprehension of the factors that govern their differentiation. Here, we show that inflammatory Mo-DCs generated in vitro expressed a large and atypical panel of C-type lectin receptors, including isoforms of CD209 and CD206, CD303 and CD207, as well as intracellular proteins at their surfaces such as the lysosomal protein CD208. Combination of these markers allowed us to identify cells in the synovial fluid of RA patients with a close phenotype of inflammatory Mo-DCs generated in vitro. Finally, we found in coculture experiments that RA synoviocytes critically affected the phenotypic differentiation of monocytes into Mo-DCs, suggesting that the crosstalk between infiltrating monocytes and local mesenchymal cells is decisive for Mo-DCs generation.

摘要

炎症性单核细胞来源的树突状细胞(Mo-DC)已在几种慢性炎症性疾病中被描述,如类风湿关节炎(RA),并被怀疑通过引发炎症和偏向适应性免疫反应而发挥有害作用。然而,其表型的特征仍然有限,以及理解控制其分化的因素也有限。在这里,我们表明,体外生成的炎症性 Mo-DC 表达了大量非典型的 C 型凝集素受体,包括 CD209 和 CD206 的同工型、CD303 和 CD207,以及其表面的细胞内蛋白,如溶酶体蛋白 CD208。这些标记物的组合使我们能够鉴定出 RA 患者滑液中的细胞,其表型与体外生成的炎症性 Mo-DC 非常相似。最后,我们在共培养实验中发现,RA 滑膜细胞严重影响单核细胞向 Mo-DC 的表型分化,表明浸润的单核细胞和局部间充质细胞之间的串扰对于 Mo-DC 的产生是决定性的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52d5/8307578/90d33a2854a0/cells-10-01663-g001.jpg

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