PPAR-γ Agonist Alleviates Liver and Spleen Pathology via Inducing Treg Cells during Schistosoma japonicum Infection.
PPAR-γ Agonist Alleviates Liver and Spleen Pathology via Inducing Treg Cells during Schistosoma japonicum Infection.
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PPAR-γ 激动剂通过在日本血吸虫感染期间诱导 Treg 细胞缓解肝脏和脾脏病理学
DOI：
10.1155/2018/6398078
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发表时间：
2018
影响因子：
4.1
通讯作者：
Ji M
中科院分区：
文献类型：
--
作者：
Zhu Y;Ni Y;Liu R;Hou M;Yang B;Song J;Sun H;Xu Z;Ji M
过氧化物酶体增殖物激活受体- (PPAR-) γ在人类代谢紊乱中起关键作用，最近被认为是细胞增殖和炎症反应的调节因子。调节性T细胞（Tregs）表达高水平的PPAR-γ蛋白，具有维持对自身抗原的免疫耐受和调节对血吸虫感染的免疫反应的能力。然而，参与解决这些反应的机制是难以捉摸的。研究了PPAR-γ激动剂吡格列酮对日本血吸虫感染小鼠肝脏和脾脏组织的影响。H&E和Masson染色检测肝脏和脾脏病变。流式细胞术检测各组小鼠肝脏和脾脏中Th1/2和Treg细胞的百分比。采用实时荧光定量PCR （RT-PCR）检测组织或细胞中PPAR-γ和Foxp3的基因表达水平。用吡格列酮体外处理巨噬细胞或与正常纯化CD4+ T细胞共培养，流式细胞术检测Treg细胞。用共免疫沉淀法检测CD4+ T细胞中PPAR-γ与Foxp3的相互作用。吡格列酮可预防肝脏和脾脏病变的发展。吡格列酮激活PPAR-γ后，日本血吸虫感染小鼠肝脏和脾脏中CD4+CD25+Foxp3+ Treg细胞百分比升高，CD3+CD4+IFN-γ+和CD3+CD4+IL-4+细胞百分比降低。此外，PPAR-γ激动剂可以在体外直接诱导Treg细胞或通过间接调节巨噬细胞的功能诱导Treg细胞。此外，通过与CD4+ T细胞中的Foxp3相互作用，PPAR-γ激动剂可以促进Foxp3的表达；然而，PPAR-γ抑制剂通过改变Foxp3和PPAR-γ的共表达来减弱Foxp3的表达。我们的研究揭示了PPAR-γ/Foxp3信号通过诱导Treg细胞调节血吸虫感染期间发生的免疫病理的先前未被认识的作用。
Peroxisome proliferator-activated receptor- (PPAR-) γ plays critical roles in human metabolic disorders and has recently been implicated as a regulator of cellular proliferation and inflammatory responses. Regulatory T cells (Tregs), which express high levels of PPAR-γ protein, have the ability to maintain immune tolerance to self-antigens and regulate immune response to Schistosoma infection. However, mechanisms involved in the resolution of these responses are elusive. Liver and spleen tissue samples in Schistosoma japonicum-infected mice after administration of pioglitazone (a PPAR-γ agonist) were collected. The hepatic and splenic pathologies were detected by H&E and Masson staining. The percentages of Th1/2 and Treg cells in the liver and spleen of each mouse were determined using flow cytometry. Levels of gene expression of PPAR-γ and Foxp3 in tissues or cells were determined using real-time PCR (RT-PCR). Macrophages were treated with pioglitazone in vitro or cocultured with normal purified CD4+ T cells for detecting Treg cells by flow cytometry. The interactions of PPAR-γ with Foxp3 in CD4+ T cells were detected by coimmunoprecipitation. Administration of pioglitazone resulted in the prevention of the development of hepatic and splenic pathologies. Activation of PPAR-γ by pioglitazone resulted in increased percentages of CD4+CD25+Foxp3+ Treg cells and decreased percentages of CD3+CD4+IFN-γ+ and CD3+CD4+IL-4+ cells in the liver and spleen of Schistosoma japonicum-infected mice. In addition, the PPAR-γ agonist can induce Treg cells in vitro directly or by modulating the macrophage's function indirectly. Furthermore, through interaction with Foxp3 in CD4+ T cells, the PPAR-γ agonist can promote the expression of Foxp3; however, the inhibitor of PPAR-γ weakened the expression of Foxp3 by modifying the coexpression of Foxp3 and PPAR-γ. Our study reveals a previously unrecognized role for PPAR-γ/Foxp3 signaling in regulating the immunopathology that occurs during Schistosoma infection through induction of Treg cells.
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影响因子：
3.7
作者：
Nausch N;Midzi N;Mduluza T;Maizels RM;Mutapi F
通讯作者：
Mutapi F
影响因子：
64.8
作者：
Herzig, S;Hedrick, S;Montminy, M
通讯作者：
Montminy, M
影响因子：
5.4
作者：
Barron, Luke;Wynn, Thomas A.
通讯作者：
Wynn, Thomas A.
影响因子：
29
作者：
Bouhlel, M. Amine;Derudas, Bruno;Chinetti-Gbaguidi, Giulia
通讯作者：
Chinetti-Gbaguidi, Giulia
影响因子：
20.1
作者：
Chawla A
通讯作者：
Chawla A