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Published on: September 1, 2015
Single-cell analysis highlights the role of CD4+ IFN-I-related T cells in Behcet's uveitis during Interferonα-2a
Meiqi Wang1, Deyu Zhang2, Xue Huang1
1Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury Repair, Zhengzhou, P. R. China.
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.

