# Apolipoprotein A-I mediates function of follicular regulatory T cells and type 2 follicular helper T in allergic rhinitis

## TL;DR

This study shows that Apolipoprotein A-I helps control immune cells involved in allergic rhinitis, suggesting it could be a new treatment target.

## Contribution

The study reveals a novel role of Apolipoprotein A-I in modulating Tfr and Tfh2 cells in allergic rhinitis.

## Key findings

- Apo-AI levels correlate with Tfr and Tfh2 cell frequencies in allergic rhinitis patients.
- Apo-AI inhibits Tfh2 cytokines and enhances Tfr suppressive function via ICOS/ICOSL pathways.
- Apo-AI knockout mice show worsened allergic responses, reversed by anti-ICOSL treatment.

## Abstract

The follicular regulatory T cells (Tfr) and type 2 follicular helper T (Tfh2) play important roles in the pathogenesis of allergic rhinitis (AR). However, its detailed mechanism underlying the regulation of between Tfr and Tfh in AR is unclear. Apolipoprotein AI (Apo-AI), a well-established anti-inflammatory protein, exhibits anti-inflammatory effects on neutrophils, monocytes, macrophages, eosinophils, and type 2 innate lymphoid cells. We sought to investigate the interaction and mechanism between Apo-AI and Tfr/Tfh2 in AR.

The peripheral Tfh2 and Tfr cells were detected and compared by flow cytometry and their correlation with serum Apo-AI protein expression were analyzed. The effect of Apo-AI on Tfh2 and Tfr cells were determined through detection of functional cytokines and key transcription factors by enzyme-linked immunosorbent assay (ELSIA) or polymerase chain reaction (PCR). A Tfr-Tfh2-B cell coculture system was adopted to investigate the role of Apo-AI. Apo-AI knockout AR mice model was established to verify the results of in vitro studies.

The serum Apo-AI concentration was positively correlated with the blood frequencies of Tfr cells and negatively correlated with the blood frequencies of Tfh2 cells in AR patients. Apo-AI inhibited IL-4 and IL-21 protein expression by Tfh2 and promoted IL-10 and TGF-beta protein expression by Tfr. In Tfr-Tfh2-B cell coculture system, Apo-AI attenuated the expression of IL-4, IL-21 and activation-induced cytidine deaminase through inducible costimulator (ICOS)/inducible costimulator ligand (ICOSL) pathways. Apo-AI partially restored the suppressive function of AR-derived Tfr cells. Apo-AI knockout AR mice presented with elevated blood Tfh2 frequencies and decreased blood Tfr frequencies, while administration of anti-ICOSL reversed the effect of Apo-AI.

Apo-AI alleviates AR through the regulation of the function of Tfh2 and Tfr, which may serve as a potential treatment target for AR.