ICOS signaling is involved in the development of allergic rhinitis by regulating the differentiation of T cells, especially Th2 cells

Abstract

Background: Inducible co-stimulator (ICOS) regulates the proliferation and differentiation of a variety of T cells. It is considered to be a potential immunotherapy target and marker for many diseases. Its dual role is worthy of further study in allergic rhinitis (AR).

Methods: We quantified ICOS-expressing T helper (Th) cells and changes in the proportions of Th1/Th2/Th9/Th17/follicular helper T (Tfh) and regulatory T cells (Treg) in the peripheral blood of patients with AR and in healthy controls (HC). All participants completed the Total Nasal Symptom Scores (TNSS) questionnaire. Ten patients with AR who underwent subcutaneous immunotherapy (SCIT) were followed for 6, 12, 24 and 36 months after treatment. In functional experiments, peripheral blood from ten dust mite-sensitized AR patients was analyzed for key T-cell subsets and ICOS expression under different stimulation conditions.

Results: The patients with AR showed higher levels of Th2, Th9, Th17 and Tfh compared with HCs, while the levels of Th1 and Treg were lower. However, ICOS expression on these T-cell subsets was elevated. TNSS correlated positively with Th2 and ICOS-expressing Th2. TNSS and ICOS-expressing Th2 decreased significantly with the passage of SCIT time. Functional assays showed that ICOS/ICOS ligand (L) stimulation increased the level of Th2, while phosphatidyl inositol-3 kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) inhibition reduced Th2 levels.

Conclusions: Our findings demonstrate that ICOS expression and effects are linked to the differentiation of T cells in AR, especially Th2 cells, which suggests ICOS-expressing Th2 cells as a potential therapeutic target for AR.