In:
Stem Cells International, Hindawi Limited, Vol. 2020 ( 2020-07-22), p. 1-12
Abstract:
Purpose . Recent evidence has shown that CD4 + T helper (Th) cells are involved in renal inflammation and fibrosis. However, whether renal fibrosis can be alleviated by intervening in the polarization of CD4 + T cells remains unknown. Our research investigated the effects of intravenously administered placenta mesenchymal stromal cells (PMSCs) or treatment with extracellular EVs (EVs) derived from PMSCs (PMSC-EVs) on the polarization of CD4 + T cells in rats with unilateral ureteral obstruction (UUO). We further verified how PMSCs affect inflammatory factor secretion and the levels of regulatory T (Treg) and Th17 CD4 + T cells in vitro. Materials and Methods . We evaluated renal interstitial inflammation and fibrosis by pathological section staining, tested the polarization of CD4 + T cells (Th17 and Treg phenotypes) by flow cytometry (FCM) and immunohistochemistry, and detected the cytokines secreted by CD4 + T cells by enzyme-linked immunosorbent assay (ELISA). Results . Compared with that of control rats, the renal tissue of PMSC-treated rats exhibited lower renal Masson scores and more Foxp3 + cell infiltration, with a significantly decreased IL17A + CD4 + T cell/CD4 + T cell ratio and a significantly elevated anti-inflammatory cytokine (IL-10) level. When CD4 + T cells were cocultured with PMSCs, CD4 + IL17A + cell percentages were decreased in a UUO model after 7 days of coculture with PMSCs. The secretion of TGF- β and IL-10 was significantly increased ( P 〈 0.05 ), while the secretion of IFN- γ , IL-17, and IL-6 was significantly decreased ( P 〈 0.05 ) in the PMSC coculture group. Moreover, after treatment with PMSC-EVs, tubulointerstitial fibrosis was alleviated, and Foxp3 + /IL-17 + cell infiltration was increased in the kidneys of UUO model animals on day 7. Conclusions . PMSCs can convert the inflammatory environment into an anti-inflammatory environment by affecting the polarization of CD4 + T cells and macrophages, inhibiting the inflammatory factors IFN- γ and IL-17, and upregulating the expression of the anti-inflammatory factors TGF- β and IL-10, ultimately leading to renal protection. Such functions may be mediated by the paracrine activity of PMSC-EVs.
Type of Medium:
Online Resource
ISSN:
1687-966X
,
1687-9678
DOI:
10.1155/2020/2685820
Language:
English
Publisher:
Hindawi Limited
Publication Date:
2020
detail.hit.zdb_id:
2573856-2
