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Background <p>T cell homeostasis is crucial for maintaining T cell population size and upcoming protective immunity in the peripheral organs. However, it remains largely unknown about the intracellular molecules and pathways beyond IL-7R signaling. Zfp335, as a key transcription factor, is involved in the multiple-stage development of thymocytes, and effector and memory T cell differentiation during immune responses.</p> Results <p>In current study, we found an upregulated expression of ZFP335 in both CD4<sup>+</sup> and CD8<sup>+</sup> T cells during peripheral homeostasis. In an adoptive transfer model, Zfp335<sup>−/−</sup> T cells failed to undergo homeostatic proliferation without survival defect. Consistently, deletion of <i>Zfp335</i> impaired T cell proliferation in in vitro culture with IL-7. Furthermore, both RNA-Sequencing and qPCR analysis showed that Zfp335 significantly affected the expression of cell cycle-related genes. Mechanistically, Zfp335 directly binds to the promoter of <i>Lmnb1</i> gene and regulates its transcription. Overexpression of <i>Lmnb1</i> significantly rescued the impaired proliferation of Zfp335<sup>−/−</sup> T cells.</p> Conclusion <p>Our results reveal a previously unrecognized role of Zfp335 in maintaining T cell homeostasis within peripheral lymphoid tissues. Specifically, Zfp335 promotes the homeostatic proliferation of naïve T cells by directly modulating the expression of the <i>Lmnb1</i> gene which ensuring the capacity of immune system.</p>

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Zinc finger protein Zfp335 is required for T cell homeostatic proliferation through regulating Lmnb1

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月14日

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  • Biao Yang,
  • Wenhua Li,
  • Xin Wang,
  • Ning Yuan,
  • Yang Gao,
  • Jiapeng Song,
  • Jun Liu,
  • Tianzhe Zhang,
  • Haiyan Liu,
  • Yuying Ren,
  • Peng Chen,
  • Xiaofeng Yang,
  • Lei Lei,
  • Xiaobo Zhou,
  • Hui Zhang,
  • Baojun Zhang

摘要

Background

T cell homeostasis is crucial for maintaining T cell population size and upcoming protective immunity in the peripheral organs. However, it remains largely unknown about the intracellular molecules and pathways beyond IL-7R signaling. Zfp335, as a key transcription factor, is involved in the multiple-stage development of thymocytes, and effector and memory T cell differentiation during immune responses.

Results

In current study, we found an upregulated expression of ZFP335 in both CD4+ and CD8+ T cells during peripheral homeostasis. In an adoptive transfer model, Zfp335−/− T cells failed to undergo homeostatic proliferation without survival defect. Consistently, deletion of Zfp335 impaired T cell proliferation in in vitro culture with IL-7. Furthermore, both RNA-Sequencing and qPCR analysis showed that Zfp335 significantly affected the expression of cell cycle-related genes. Mechanistically, Zfp335 directly binds to the promoter of Lmnb1 gene and regulates its transcription. Overexpression of Lmnb1 significantly rescued the impaired proliferation of Zfp335−/− T cells.

Conclusion

Our results reveal a previously unrecognized role of Zfp335 in maintaining T cell homeostasis within peripheral lymphoid tissues. Specifically, Zfp335 promotes the homeostatic proliferation of naïve T cells by directly modulating the expression of the Lmnb1 gene which ensuring the capacity of immune system.