Single-cell Analysis of TFH Cell Subsets in Allergic Rhinitis: Discovery
of the GZMK+ TFH Cell Subset
Abstract
Background: Allergic rhinitis (AR) is a prevalent condition
linked to IgE-mediated immune responses. T follicular helper (TFH)
cells, particularly the TFH2 subset, have been implicated in the
pathogenesis of AR due to their role in promoting IgE production.
However, the number, functional gene expression, and differences among
the three TFH subsets in AR patients remain unclear. Methods:
This study recruited six AR patients and three healthy controls. Flow
cytometry and single-cell sequencing were used to identify and analyze
subsets of TFH cells. TFH1, TFH2, and TFH17 subsets were identified
based on CXCR3 and CXCR6 expression. Functional gene expression in TFH
subsets of AR patients and healthy controls was analyzed to explore
differences in immune responses. Results: AR patients exhibited
a significant increase in circulating TFH2 cells compared to healthy
controls, correlating with disease severity. Additionally, precursor
memory TFH cells were higher in AR patients. However, no significant
differences were found in the expression of functional membrane
molecules on TFH cells between the two groups.. Single-cell RNA
sequencing revealed nine TFH clusters with differential expression of
functional genes, including a GZMK + TFH subset. The
increased proportion of TFH1 and TFH2 subsets in AR compared to controls
suggests their significant involvement in the pathogenesis of AR.
Conclusions: Our study reveals increased TFH2 cells and
differential TFH subset distributions in AR patients, especially the
discovery of the GZMK + TFH subset, providing insights
into TFH-mediated mechanisms in AR. These findings suggest potential
therapeutic targets for AR treatment.