PPAR-γ Agonist Alleviates Liver and Spleen Pathology via Inducing Treg Cells during Schistosoma japonicum Infection

• Published in: Journal of immunology research Vol. 2018; no. 2018; pp. 1 - 11
• Main Authors: Ji, Minjun, Xu, Zhipeng, Song, Jingwei, Yang, Bingya, Hou, Min, Liu, Ran, Ni, Yangyue, Zhu, Yuxiao, Sun, Hongzhi
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2018; Hindawi; John Wiley & Sons, Inc; Wiley
• Subjects: Agonists; Animals; Antigens; Autoantigens; CD25 antigen; CD3 antigen; CD4 antigen; Cell proliferation; Eggs; Flow cytometry; Foxp3 protein; Gene expression; Gene flow; Hepatocytes; Immunological tolerance; Immunology; Immunoregulation; Infections; Inflammation; Insulin resistance; Interleukin 4; Liver; Liver - drug effects; Liver - pathology; Lymphocytes; Lymphocytes T; Macrophages; Metabolic disorders; Mice; Mice, Inbred C57BL; Pathology; Peroxisome proliferator-activated receptors; Pioglitazone; Polymerase chain reaction; PPAR gamma - agonists; Regulation; Rodents; Schistosoma; Schistosoma japonicum; Schistosomiasis japonica - immunology; Schistosomiasis japonica - pathology; Spleen; Spleen - drug effects; Spleen - pathology; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; Thiazolidinediones - pharmacokinetics; Tropical diseases; Tumor necrosis factor-TNF; γ-Interferon; United States > US
• ISSN: 2314-8861; 2314-7156; 2314-7156
• DOI: 10.1155/2018/6398078

Background. 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. Methods. 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. Results. 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. Conclusions. 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.