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在 IgA 肾病患者中，浆细胞样树突状细胞的丰度增加和干扰素-α诱导浆细胞分化。

Increased Abundance of Plasmacytoid Dendritic Cells and Interferon-Alpha Induces Plasma Cell Differentiation in Patients of IgA Nephropathy.

机构信息

Translational Medical Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Department of Nephrology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

出版信息

Mediators Inflamm. 2017;2017:4532409. doi: 10.1155/2017/4532409. Epub 2017 Dec 18.

DOI:10.1155/2017/4532409
PMID:29403161
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5748321/
Abstract

The roles of pDC and IFN- have not been well defined in IgA nephropathy (IgAN). In this study, we investigated the abundance of pDCs and IFN- in IgAN patients and the response of peripheral blood mononuclear cells (PBMCs) after stimulation of the pDC-preferred TLR9 ligand CpG2216. The effects of IFN- on plasma cell differentiation and leukocyte migration were also investigated. Here, we found that the percentages of pDCs were increased in PBMCs of IgAN patients, than in those of healthy controls. Plasma levels of IFN- proteins and abundance of plasma cells were higher in IgAN patients than in healthy donors. Plasma IFN- levels were positively associated with proteinuria, renal IgM deposition, and renal tubular atrophy/interstitial fibrosis grade in IgAN patients. Ex vivo activation of TLR9 on pDCs resulted in increased IFN- production and enhanced plasma cell differentiation in IgAN patients as compared with healthy donors. IFN- treatment led to increased plasma cell differentiation . IFN- also significantly promoted expression of chemokines IP-10 and MCP-1 in human mesangial cells, which subsequently facilitated the transendothelial migration of human CD4 and CD14 cells. In conclusion, pDC and its secreted cytokine IFN- may play important roles in pathological changes of IgA nephropathy.

摘要

pDC 和 IFN- 在 IgA 肾病（IgAN）中的作用尚未得到很好的定义。在这项研究中，我们研究了 IgAN 患者中 pDC 和 IFN- 的丰度，以及 pDC 优先 TLR9 配体 CpG2216 刺激后外周血单核细胞（PBMC）的反应。还研究了 IFN- 对浆细胞分化和白细胞迁移的影响。在这里，我们发现 IgAN 患者 PBMC 中的 pDC 比例高于健康对照组。IgAN 患者的血浆 IFN- 蛋白水平和浆细胞丰度均高于健康供体。IgAN 患者的血浆 IFN- 水平与蛋白尿、肾 IgM 沉积和肾小管萎缩/间质纤维化程度呈正相关。与健康供体相比，TLR9 在 pDC 上的体外激活导致 IgAN 患者 IFN- 产生增加和浆细胞分化增强。IFN- 治疗导致浆细胞分化增加。IFN- 还显著促进了人系膜细胞中趋化因子 IP-10 和 MCP-1 的表达，随后促进了人 CD4 和 CD14 细胞的跨内皮迁移。总之，pDC 及其分泌的细胞因子 IFN- 可能在 IgA 肾病的病理变化中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa79/5748321/9522481e3bce/MI2017-4532409.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa79/5748321/b7ca0f3e5415/MI2017-4532409.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa79/5748321/e62deb053403/MI2017-4532409.004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa79/5748321/ba5d64e44f3d/MI2017-4532409.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa79/5748321/9522481e3bce/MI2017-4532409.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa79/5748321/b7ca0f3e5415/MI2017-4532409.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa79/5748321/2b8f458e52c7/MI2017-4532409.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa79/5748321/c1421453d530/MI2017-4532409.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa79/5748321/e62deb053403/MI2017-4532409.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa79/5748321/7dd9d321e508/MI2017-4532409.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa79/5748321/ba5d64e44f3d/MI2017-4532409.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa79/5748321/9522481e3bce/MI2017-4532409.007.jpg

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