Circulating TFH2 Cell Expansion and GZMK⁺ TFH1 Cells are Associated with Allergic Rhinitis

Area of Science:

• Immunology
• Allergy Research
• Cellular Biology

Background:

• Allergic rhinitis (AR) is an IgE-mediated immune response.
• T follicular helper (TFH) cells, particularly TFH2, are linked to type 2 immunity in AR.
• The broader impact on TFH subsets, including TFH1, in AR is not fully understood.

Purpose of the Study:

• To investigate the heterogeneity of circulating TFH (cTFH) subsets in allergic rhinitis.
• To determine if AR involves isolated TFH2 expansion or broader TFH remodeling.
• To explore the transcriptional landscape of TFH cells in AR.

Main Methods:

• Compared cTFH subsets and activation states in AR patients and healthy controls using flow cytometry.
• Employed single-cell RNA sequencing (scRNA-seq) to analyze TFH transcriptional heterogeneity in an exploratory cohort.
• Correlated cTFH frequencies with AR disease severity.

Main Results:

• Significantly increased cTFH2 cell frequencies and enhanced TFH activation were observed in AR patients.
• scRNA-seq identified six distinct TFH clusters, with TFH2 signatures enriched in AR.
• A GZMK+ TFH1 subset, expressing cytotoxic genes, was more abundant in AR patients.

Conclusions:

• AR is characterized by the expansion of both cTFH2 and GZMK+ TFH1 subsets.
• This study highlights the phenotypic and transcriptional heterogeneity of cTFH cells in AR.
• Peripheral TFH profiling may help characterize systemic immune alterations in allergic inflammation.