Analysis of TNF-mediated recruitment and activation of glomerular dendritic cells in mouse kidneys by compartment-specific flow cytometry.

Analysis of TNF-mediated recruitment and activation of glomerular dendritic cells in mouse kidneys by compartment-specific flow cytometry.
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通过区室特异性流式细胞术分析小鼠肾脏中 TNF 介导的肾小球树突状细胞的募集和激活

DOI:
10.1038/ki.2013.46
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发表时间:
2013
影响因子:
19.6
通讯作者:
Vielhauer V
Vielhauer V
中科院分区:
医学1区
文献类型:
--
作者:
Schwarz M;Taubitz A;Eltrich N;Mulay SR;Allam R;Vielhauer V

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肾脏树突状细胞(DC)形成间质网络,有助于肾脏中的炎症和适应性免疫反应。DC样肾小球CD11c+单核吞噬细胞的存在和功能作用是一个有争议的问题。使用隔室特异性流式细胞术,我们发现,健康小鼠肾脏含有1.3 CD11c+细胞每100个肾小球和这些增加了4.6倍和13倍后,TNF刺激和免疫复合物沉积,分别。隔室特异性mRNA表达显示,主要是肾小球表达的TNF受体,趋化因子和粘附分子,所有上调TNF暴露后。腹腔注射TNF可诱导中性粒细胞和单核吞噬细胞(包括DC样CD11c+细胞)流入肾小球和肾小管间质,但在TNF受体(Tnfr)1缺陷小鼠中减少。此外,Tnfr2缺乏损害肾小球浸润的CD11c+细胞,但不是中性粒细胞。在Tnfr 1或Tnfr 2存在的情况下,间质CD 11 c+细胞浸润。TNF暴露也诱导了肾小球和间质CD11c+细胞的类似成熟,如通过增加MHC II、CD54和共刺激分子CD40、CD80和CD86的表面表达所证明的。因此,通过隔室特异性流式细胞术,我们可以证明正常小鼠肾小球中DC样CD11c+单核吞噬细胞的组成性存在及其TNF诱导的积累和激活。
Renal dendritic cells (DCs) form an interstitial network contributing to inflammatory and adaptive immune responses in the kidney. The presence and functional role of DC-like glomerular CD11c+mononuclear phagocytes is a matter of debate. Using compartment-specific flow cytometry we found that healthy mouse kidneys contained 1.3 CD11c+cells per 100 glomeruli and these increased by 4.6-fold and 13-fold after TNF stimulation and immune complex deposition, respectively. Compartment-specific mRNA expression revealed a predominantly glomerular expression of TNF receptors, chemokines, and adhesion molecules; all upregulated after TNF exposure. Intraperitoneal TNF injection induced influx of neutrophils and mononuclear phagocytes including DC-like CD11c+cells into both the glomerular and tubulointerstitial compartments, but reduced in TNF receptor (Tnfr) 1-deficient mice. Additionally, Tnfr2 deficiency impaired glomerular infiltration of CD11c+cells, but not neutrophils. Interstitial CD11c+cells infiltrated in the presence of Tnfr1 or Tnfr2. TNF exposure also induced similar maturation of glomerular and interstitial CD11c+cells as demonstrated by increased surface expression of MHC II, CD54, and costimulatory molecules CD40, CD80, and CD86. Thus, by compartment-specific flow cytometry we could demonstrate the constitutive presence of DC-like CD11c+mononuclear phagocytes in normal mouse glomeruli and their TNF-induced accumulation and activation.
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