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Th 细胞因子 mRNA 表达在不同形式肾小球肾炎中的各种作用。

Various roles of Th cytokine mRNA expression in different forms of glomerulonephritis.

机构信息

Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.

出版信息

Am J Nephrol. 2013;38(2):115-23. doi: 10.1159/000353102. Epub 2013 Jul 30.

DOI:10.1159/000353102
PMID:23920047
Abstract

BACKGROUND

Kidney disease is characterized by injurious immune responses to self or foreign antigens. The development and maintenance of immune responses generally involves activation of T lymphocytes. We evaluated mRNA expression patterns of T-cell cytokines to identify the principal Th-cell subset involved in the development of antineutrophil cytoplasmic antigen-associated pauci-immune crescentic glomerulonephritis (ANCAGN), membranoproliferative glomerulonephritis (MPGN), and membranous nephropathy (MN).

METHODS

Kidney biopsy specimens from ANCAGN (17), MPGN (11), and MN (14) patients were evaluated for mRNA expression of various T-cell cytokines.

RESULTS

Interferon-γ mRNA expression was detected in both ANCAGN and MPGN, but not in MN patients. Furthermore, mRNA expression of interleukin (IL)-12, a Th1-associated cytokine, was lower in MN patients than in ANCAGN and MPGN patients. In contrast, a significantly higher expression of IL-4 and IL-5 was observed in MN than in ANCAGN and MPGN patients. In the analyses of Th17-associated cytokine expression, a significantly higher expression of IL-6 and IL-17 was observed in ANCAGN than in MPGN and MN patients. No significant differences were observed in the expression of these cytokines between MPGN and MN patients. With regard to Treg-associated cytokines, a significantly higher IL-10 expression was observed in MN than in ANCAGN patients, and a significantly higher transforming growth factor-β expression was observed in MN than in ANCAGN and MPGN patients. Similarly, Foxp3 expression was significantly higher in MN.

CONCLUSION

Th1 and Th17 immune responses in ANCAGN, the Th1 response in MPGN, and Th2 and Treg responses in MN patients may be integral for the distinct histological features of these diseases.

摘要

背景

肾脏疾病的特征是对自身或外来抗原产生损伤性免疫反应。免疫反应的发展和维持通常涉及 T 淋巴细胞的激活。我们评估了 T 细胞细胞因子的 mRNA 表达模式,以确定参与抗中性粒细胞胞质抗体相关性少免疫性新月体性肾小球肾炎(ANCAGN)、膜增生性肾小球肾炎(MPGN)和膜性肾病(MN)发展的主要 Th 细胞亚群。

方法

评估了 ANCAGN(17 例)、MPGN(11 例)和 MN(14 例)患者的肾活检标本中各种 T 细胞细胞因子的 mRNA 表达。

结果

IFN-γ mRNA 表达在 ANCAGN 和 MPGN 中均有检测到,但在 MN 患者中没有检测到。此外,MN 患者的 Th1 相关细胞因子 IL-12 的 mRNA 表达低于 ANCAGN 和 MPGN 患者。相比之下,MN 患者的 IL-4 和 IL-5 表达明显高于 ANCAGN 和 MPGN 患者。在 Th17 相关细胞因子表达分析中,IL-6 和 IL-17 的表达在 ANCAGN 中明显高于 MPGN 和 MN 患者。在 MPGN 和 MN 患者之间,这些细胞因子的表达没有观察到显著差异。在 Treg 相关细胞因子方面,IL-10 在 MN 患者中的表达明显高于 ANCAGN 患者,转化生长因子-β在 MN 患者中的表达明显高于 ANCAGN 和 MPGN 患者。同样,Foxp3 在 MN 患者中的表达明显更高。

结论

ANCAGN 中的 Th1 和 Th17 免疫反应、MPGN 中的 Th1 反应以及 MN 患者中的 Th2 和 Treg 反应可能是这些疾病的独特组织学特征的组成部分。

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