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Background <p>Human umbilical cord mesenchymal stem cells (HUMSCs) are effective therapies for inflammatory bowel disease. However, the mechanisms remain unresolved. We found HUMSCs express CD126 (IL-6 receptor), which indicated CD126 sub-populations might show a distinct response to inflammation. In the present study, we explored whether CD126 is a critical molecule for HUMSCs in regulating inflammation.</p> Methods <p>We assessed the regulatory effects of CD126 high (CD126<sup>hi</sup>) on the T lymphocyte subpopulations and related cytokines in the dextran sulfate sodium (DSS)-induced colitis model. The effect of CD126<sup>hi</sup> was evaluated by Hematoxylin and Eosin (H&amp;E) staining, fluorescence-activated cell sorting (FACS), and enzyme-linked immunosorbent assay (ELISA) analyses. Statistical significance was typically determined using Student’s t-test or one-way analysis of variance (ANOVA) with Tukey test.</p> Results <p>The disease symptoms were markedly ameliorated and the interleukin-6 (IL-6), interleukin-17 (IL-17), interferon-γ (IFN-γ), Tumor necrosis factor-α (TNF-α), and interleukin-4 (IL-4) levels were significantly reduced in DSS-treated mice administered with CD126<sup>hi</sup> HUMSCs but not in DSS-treated mice administered with CD126 low (CD126<sup>lo</sup>) HUMSCs. Intriguingly, CD126<sup>hi</sup> HUMSCs significantly increased the levels of transforming growth factor-β (TGF-β1) and interleukin-10 (IL-10) in DSS-treated mice, accompanied by an increase in regulatory T cells (Treg cells). In vitro experiments showed that CD126<sup>hi</sup> HUMSCs secreted TGF-β1 in response to IL-6 stimulation, while CD126<sup>lo</sup> HUMSCs were latent in the inflammatory environment. We considered that TGF-β1 secreted by CD126<sup>hi</sup> HUMSCs regulated the balance of Treg cells and thus promoted the recovery of murine colitis.</p> Conclusion <p>Our results revealed a mechanism wherein CD126<sup>hi</sup> HUMSCs function as inflammatory sensors and secrete anti-inflammatory cytokines to rebalance the population of T cells. This study shed light on the potential therapeutic application of CD126<sup>hi</sup> HUMSCs for inflammatory diseases such as inflammatory bowel disease.</p>

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CD126hi umbilical cord mesenchymal stem cells sensitive to IL-6 ameliorate inflammatory bowel disease by producing TGF-β1

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月27日

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  • Yanxia Fu,
  • Bingchen Xie,
  • Yinyin Wang,
  • Jianqiu Sheng,
  • Zhijie Chang,
  • Xiaojue Qiu,
  • Dongliang Yu,
  • Junfeng Xu

摘要

Background

Human umbilical cord mesenchymal stem cells (HUMSCs) are effective therapies for inflammatory bowel disease. However, the mechanisms remain unresolved. We found HUMSCs express CD126 (IL-6 receptor), which indicated CD126 sub-populations might show a distinct response to inflammation. In the present study, we explored whether CD126 is a critical molecule for HUMSCs in regulating inflammation.

Methods

We assessed the regulatory effects of CD126 high (CD126hi) on the T lymphocyte subpopulations and related cytokines in the dextran sulfate sodium (DSS)-induced colitis model. The effect of CD126hi was evaluated by Hematoxylin and Eosin (H&E) staining, fluorescence-activated cell sorting (FACS), and enzyme-linked immunosorbent assay (ELISA) analyses. Statistical significance was typically determined using Student’s t-test or one-way analysis of variance (ANOVA) with Tukey test.

Results

The disease symptoms were markedly ameliorated and the interleukin-6 (IL-6), interleukin-17 (IL-17), interferon-γ (IFN-γ), Tumor necrosis factor-α (TNF-α), and interleukin-4 (IL-4) levels were significantly reduced in DSS-treated mice administered with CD126hi HUMSCs but not in DSS-treated mice administered with CD126 low (CD126lo) HUMSCs. Intriguingly, CD126hi HUMSCs significantly increased the levels of transforming growth factor-β (TGF-β1) and interleukin-10 (IL-10) in DSS-treated mice, accompanied by an increase in regulatory T cells (Treg cells). In vitro experiments showed that CD126hi HUMSCs secreted TGF-β1 in response to IL-6 stimulation, while CD126lo HUMSCs were latent in the inflammatory environment. We considered that TGF-β1 secreted by CD126hi HUMSCs regulated the balance of Treg cells and thus promoted the recovery of murine colitis.

Conclusion

Our results revealed a mechanism wherein CD126hi HUMSCs function as inflammatory sensors and secrete anti-inflammatory cytokines to rebalance the population of T cells. This study shed light on the potential therapeutic application of CD126hi HUMSCs for inflammatory diseases such as inflammatory bowel disease.