In:
Journal of Immunology Research, Hindawi Limited, Vol. 2018 ( 2018-07-17), p. 1-11
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
2314-8861
,
2314-7156
DOI:
10.1155/2018/6398078
Language:
English
Publisher:
Hindawi Limited
Publication Date:
2018
detail.hit.zdb_id:
2817541-4
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