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Objectives <p>Research indicates that low doses of interleukin-2 (IL-2) can effectively mitigate Rheumatoid arthritis (RA) symptoms by promoting Treg cells, while high doses may enhance immune responses and exacerbate the disease. Consequently, this study employed mutated IL-2 to minimize its impact on CD8<sup>+</sup> T and NK cell activation while preserving its influence on Treg cells.</p> Methods <p>We used a previously published mutation sites to construct the murine IL-2 mutants by overlap PCR. Then we assessed its impact on the proliferation and functionality of Treg cells by flow cytometry and PCR. The synergistic effects of mutated IL-2 and MSC on collagen-induced arthritis (CIA) in mice were evaluated through the infusion of lentiviral-transduced umbilical cord-derived mesenchymal stromal cell (UC-MSC) for CIA treatment and through pathological section staining to assess inflammatory joint injury, cartilage destruction, and osteoclast infiltration.</p> Results <p>Mutant IL-2 demonstrated targeted enhancement of both the proportion and proliferative activity of Treg cells with a diminished capacity to stimulate the proliferation of CD8<sup>+</sup> T cells and NK cells relative to wild-type IL-2. Moreover, MSC-mutant IL-2 significantly augmented the proportion of Treg cells compared to either MSC or mutant IL-2 in isolation. Treatment with MSC-mutant IL-2 infusion in CIA mice ameliorated arthritis symptoms and reduced inflammatory infiltration and cartilage damage in their joints.</p> Conclusion <p>Mutant IL-2 enhances Treg function and proliferation while exerting reduced effects on CD8<sup>+</sup> T and NK cell activation. MSC expressing mutant IL-2 demonstrates therapeutic benefits in CIA by increasing the proportion of Treg cells and reducing the proportion of CD8<sup>+</sup> T cells.</p>

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Mutant IL-2-expressing mesenchymal stromal cells promote regulatory T cells proliferation and activation in collagen induced arthritis mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月8日

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  • Zhicheng Tang,
  • Fan Yang,
  • Jingyi Shen,
  • Haolin Wu,
  • Huiming Hong,
  • Yue Wang,
  • Fanzhang Yin,
  • Xiaojun Tang,
  • Huayong Zhang

摘要

Objectives

Research indicates that low doses of interleukin-2 (IL-2) can effectively mitigate Rheumatoid arthritis (RA) symptoms by promoting Treg cells, while high doses may enhance immune responses and exacerbate the disease. Consequently, this study employed mutated IL-2 to minimize its impact on CD8+ T and NK cell activation while preserving its influence on Treg cells.

Methods

We used a previously published mutation sites to construct the murine IL-2 mutants by overlap PCR. Then we assessed its impact on the proliferation and functionality of Treg cells by flow cytometry and PCR. The synergistic effects of mutated IL-2 and MSC on collagen-induced arthritis (CIA) in mice were evaluated through the infusion of lentiviral-transduced umbilical cord-derived mesenchymal stromal cell (UC-MSC) for CIA treatment and through pathological section staining to assess inflammatory joint injury, cartilage destruction, and osteoclast infiltration.

Results

Mutant IL-2 demonstrated targeted enhancement of both the proportion and proliferative activity of Treg cells with a diminished capacity to stimulate the proliferation of CD8+ T cells and NK cells relative to wild-type IL-2. Moreover, MSC-mutant IL-2 significantly augmented the proportion of Treg cells compared to either MSC or mutant IL-2 in isolation. Treatment with MSC-mutant IL-2 infusion in CIA mice ameliorated arthritis symptoms and reduced inflammatory infiltration and cartilage damage in their joints.

Conclusion

Mutant IL-2 enhances Treg function and proliferation while exerting reduced effects on CD8+ T and NK cell activation. MSC expressing mutant IL-2 demonstrates therapeutic benefits in CIA by increasing the proportion of Treg cells and reducing the proportion of CD8+ T cells.