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AB0177 Human Umbilical Cord Mesenchymal Stem Cells Inhibit Follicular Helper T Cell Expansion in B6.Mrl-Faslpr Lupus Mice
  1. Z. Zhang,
  2. X. Feng,
  3. W. Deng,
  4. S. Huang,
  5. G. Yao,
  6. W. Chen,
  7. L. Sun
  1. Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China

Abstract

Background Follicular helper T (Tfh) cells have been implicated in the pathogenesis of autoimmune diseases. Human umbilical cord mesenchymal stem cell (hUC-MSC). Transplantation could alleviate disease progression in both lupus mice and patients. However, the mechanism is largely unknown.

Objectives The objective of this study was to explore modulatory effects of hUC-MSCs on Tfh cells in B6.MRL-Faslpr lupus mice.

Methods The percentages of spleen Tfh cells in B6.MRL-Faslpr lupus mice and C57BL/6 (B6) mice were examined by flow cytometry. Serum IL-21 levels were measured by ELISA. The correlations between the percentage of spleen Tfh cells, serum IL-21 concentrations and lupus-related manifestations of B6.MRL-Faslpr mice were analyzed by Pearson's correlation test respectively. CD4+ T cells were isolated from the spleen of B6.MRL-Faslpr mice and cocultured with hUC-MSCs for 3 days at different ratios (100:1, 20:1, 4:1), and then the frequencies of CD4+CXCR5+PD-1+T cells were determined by flow cytometry. The differentiation, proliferation and apoptosis of Tfh cells were also analyzed by flow cytometry after cocultured with hUC-MSCs. 1×106 hUC-MSCs were injected into B6.MRL-Faslpr lupus mice via tail vein and the control groups were administered with 1×106 fibroblast-like synoviocytes (FLSs) and PBS respectively. 4 weeks later, all the mice were sacrificed. The percentages of spleen Tfh cells and plasma cells were examined by flow cytometry. CD4+CXCR5+Tfh cells were isolated from spleens of all the administered mice and cocultured with B220+cells isolated from spleens of B6 mice. 5 days later, IgG level of the coculture supernatants were measured by ELISA.

Results The percentages of spleen Tfh cells and serum IL-21 concentrations in lupus mice were significantly higher than those in B6 mice. Both the frequencies of spleen Tfh cells and serum IL-21 levels were positively correlated with serum IgG, ANA and ds-DNA antibody levels in lupus mice. HUC-MSCs could suppress Tfh generation when cocultured with CD4+T cells at different ratios. The differentiation, proliferation and apoptosis of Tfh cells could all be inhibited by hUC-MSCs in vitro. 4 weeks after hUC-MSC transplantation, the percentages of spleen Tfh cells and plasma cells were significantly lower than those in control groups. Supernatants of B220+cells cocultured with CD4+CXCR5+Tfh cells isolated from spleens of hUC-MSC treated lupus mice had lower levels of IgG than control groups.

Conclusions HUC-MSCs could inhibit Tfh expansion in B6.MRL-Faslpr lupus mice, which may be a mechanism of hUC-MSC transplantation alleviating lupus.

Disclosure of Interest None declared

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