Single-cell transcriptomic profiling reveals aberrant CD4⁺ naive T cell differentiation driving immune activation in...

Area of Science:

• Immunology
• Ophthalmology
• Cellular Biology

Background:

• Behçet's uveitis (BU) is a severe ocular inflammation in Behçet's disease.
• It involves T cell dysregulation but underlying mechanisms are unclear.

Purpose of the Study:

• To elucidate the mechanisms of T cell dysfunction and immune activation in BU.
• To identify potential therapeutic targets for BU.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) of PBMCs from BU patients and controls.
• Integration with aqueous humor (AH) single-cell data.
• Validation via qPCR, flow cytometry, and functional assays.

Main Results:

• Depletion of naive CD4+ T cells in BU patients, differentiating into IL-32 and CXCR4-expressing effector cells.
• IL-32 drives Th1/Th17 polarization; pseudotime analysis shows progression to inflammatory Th17-like cells in AH.
• CXCR4 mediates T cell ocular migration; macrophage-T cell crosstalk via MIF signaling identified.

Conclusions:

• A coordinated mechanism links systemic T cell issues to ocular inflammation in BU.
• Targeting IL-32 and CXCR4 shows promise for immune restoration and preventing BU-related tissue damage.