Interferon-纬 and tumor necrosis factor-伪 promote the ability of human placenta-derived mesenchymal stromal cells to express programmed death ligand-2 and induce the differentiation of CD4⁺interleukin-10⁺ and CD8⁺interleukin-10⁺Treg subsets

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• 作者：Heng Li¹ ; ^&lowast ; ; Weiwei Wang¹ ; ^&lowast ; ; Guoyan Wang² ; Yun Hou³ ; Fenghuang Xu¹ ; Ranran Liu⁴ ; Feifei Wang⁵ ; Jiangnan Xue¹ ; Tao Hu¹ ; Xiying Luan¹ ; ^{xyluan@sohu.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：human placenta ; IFN-纬 ; mesenchymal stromal cells ; PDL2 ; TNF-伪 ; Treg subsets
• 刊名：Cytotherapy
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：17
• 期：11
• 页码：1560-1571
• 全文大小：1510 K

文摘

Mesenchymal stromal cells (MSCs) and regulatory T cells (Treg) have been successfully used in treating autoimmune diseases accompanied by abundant inflammatory cytokines such as interferon (IFN)-纬 and tumor necrosis factor (TNF)-伪. Therefore, this work investigated the effects of IFN-纬 and TNF-伪 on the ability of human placenta-derived mesenchymal stromal cells (hPMSCs) on inducing the differentiation of CD4⁺interleukin (IL)-10⁺and CD8⁺IL-10⁺Treg subsets.

Methods

Human PMSCs were co-cultured with T cells in the presence or absence of a trans-well system or anti- programmed death ligand-2 (PDL2) monoclonal antibody (mAb), respectively. CD4⁺IL-10⁺and CD8⁺IL-10⁺Treg subsets, as well as the levels of IL-10 in the supernatants, were detected on this basis. Examinations were conducted to explore the impact of IFN-纬 and TNF-伪 on the expression of PDL2 in hPMSCs. In this process, flow cytometry, Western blot and reverse-transcriptase–polymerase chain reaction were used.

Results

CD4⁺IL-10⁺and CD8⁺IL-10⁺Treg subsets from T cells either non-activated or activated by use of phytohaemagglutinin (PHA) or CD3/CD28mAb significantly increased in the presence of hPMSCs. However, these levels markedly decreased after blocking the expression of PDL2 in hPMSCs. IL-10 followed the same pattern. Furthermore, the percentages of CD4⁺IL-10⁺ and CD8⁺IL-10⁺T cells also sharply declined under the trans-well system, whereas the percentages as well as the expression of PDL2 in hPMSCs oppositely raised after hPMSCs pre-stimulated by IFN-纬 and TNF-伪. IFN-纬 could promote the expression of PDL2 partly through the JAK/STAT signaling pathway.

Conclusions

IFN-纬 and TNF-伪 could promote the ability of hPMSCs in inducing the differentiation of CD4⁺IL-10⁺and CD8⁺IL-10⁺Treg subsets and enhance the expression of PDL2 in hPMSCs. These would benefit the application of hPMSCs in clinical trials.