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Background <p>Behcet’s disease (BD) involves multiple immune cells, but the mechanism by which interferon α-2a (IFNα-2a) exerts therapeutic effects on BD through immune cell modulation remains unclear. This study aimed to investigate the role of CD4 + IFN-I-related T cells in BD with active uveitis during IFNα-2a therapy.</p> Methods <p>A single-cell atlas of peripheral blood mononuclear cells (PBMCs) was constructed from BD patients with active uveitis, post-4-month IFNα-2a therapy BD patients, active BD patients, and healthy controls (HCs) by integrating in-house and public scRNA-seq data. Bulk mRNA sequencing of CD4 + T cells from active BD patients and HCs was performed for validation. Cell-cell interaction, in vitro coculture, and inhibitor experiments were used to explore the underlying mechanisms.</p> Results <p>CD4 + IFN-I-related T cells (characterized by high interferon-related gene expression) were significantly decreased in active BD patients but restored after IFNα-2a therapy. The LLT1-CD161 interaction intensity between CD4 + IFN-I-related T cells and NK cells was reduced in active BD and recovered post-therapy. CD4 + IFN-I-related T cells inhibited NK cell activation and IFN-γ secretion via the CD161 receptor.</p> Conclusions <p>IFNα-2a therapy reverses the decreased frequency of CD4 + IFN-I-related T cells in active BD, which in turn inhibits the inflammatory phenotype of NK cells through LLT1-CD161 interaction, providing new insights into the therapeutic mechanism of IFNα-2a in BD.</p>

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Single-cell analysis highlights the role of CD4+ IFN-I-related T cells in Behcet’s uveitis during Interferonα-2a therapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月22日

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  • Meiqi Wang,
  • Deyu Zhang,
  • Xue Huang,
  • Zhenyu Zhong,
  • Qingfeng Wang,
  • Huan Liu,
  • Guannan Su,
  • Shixiang Jing,
  • Tao Yang,
  • Na Li,
  • Peizeng Yang

摘要

Background

Behcet’s disease (BD) involves multiple immune cells, but the mechanism by which interferon α-2a (IFNα-2a) exerts therapeutic effects on BD through immune cell modulation remains unclear. This study aimed to investigate the role of CD4 + IFN-I-related T cells in BD with active uveitis during IFNα-2a therapy.

Methods

A single-cell atlas of peripheral blood mononuclear cells (PBMCs) was constructed from BD patients with active uveitis, post-4-month IFNα-2a therapy BD patients, active BD patients, and healthy controls (HCs) by integrating in-house and public scRNA-seq data. Bulk mRNA sequencing of CD4 + T cells from active BD patients and HCs was performed for validation. Cell-cell interaction, in vitro coculture, and inhibitor experiments were used to explore the underlying mechanisms.

Results

CD4 + IFN-I-related T cells (characterized by high interferon-related gene expression) were significantly decreased in active BD patients but restored after IFNα-2a therapy. The LLT1-CD161 interaction intensity between CD4 + IFN-I-related T cells and NK cells was reduced in active BD and recovered post-therapy. CD4 + IFN-I-related T cells inhibited NK cell activation and IFN-γ secretion via the CD161 receptor.

Conclusions

IFNα-2a therapy reverses the decreased frequency of CD4 + IFN-I-related T cells in active BD, which in turn inhibits the inflammatory phenotype of NK cells through LLT1-CD161 interaction, providing new insights into the therapeutic mechanism of IFNα-2a in BD.