SO₂ activates Th17 cells through the JAK1,2/STAT3 signaling pathway

Area of Science:

• Immunology
• Environmental Health
• Molecular Biology

Background:

• Allergic rhinitis (AR) involves complex immune responses.
• Sulfur dioxide (SO2) is a known environmental pollutant with potential immunomodulatory effects.
• The role of T-helper (Th) cells, specifically Th1, Th2, and Th17, and the JAK/STAT signaling pathway in AR pathogenesis requires further elucidation.

Purpose of the Study:

• To investigate the impact of SO2 exposure on Th1, Th2, and Th17 cell populations in individuals with AR.
• To explore the involvement of the Janus kinase (JAK) 1, 2/signal transducer and activator of transcription (STAT) 3 signaling pathway in SO2-induced immune responses.
• To identify potential therapeutic targets for AR treatment.

Main Methods:

• Peripheral blood mononuclear cells (PBMCs) from AR patients and healthy controls were cultured and stimulated with SO2 derivatives.
• Flow cytometry was used to analyze Th cell subsets (Th1, Th2, Th17, Treg) and cytokine expression.
• Quantitative real-time PCR (qRT-PCR) and Western blot analysis were employed to assess gene and protein expression of key cytokines and signaling molecules (JAK1, JAK2, STAT3, RORγt).
• The JAK inhibitor Ruxolitinib was used to probe the JAK/STAT pathway's role.

Main Results:

• SO2 stimulation upregulated Th1, Th2, and Th17 cells and associated cytokines in both AR patients and healthy individuals.
• Elevated levels of IL-17A, RORγt, and IL-6 were observed, alongside increased JAK1, JAK2, STAT3, and RORγt expression in Jurkat cells upon SO2 exposure.
• Ruxolitinib treatment inhibited the JAK/STAT pathway, significantly reducing Th17 cell counts, IL-17A levels, and RORγt expression, indicating SO2's effect on Th17 differentiation is mediated by JAK/STAT signaling.

Conclusions:

• SO2 exposure exacerbates Th1/Th2/Th17 inflammation in AR and can induce Th1 and Th17 inflammation in healthy individuals.
• The JAK/STAT signaling pathway plays a crucial role in mediating SO2-induced Th17 cell differentiation and inflammation.
• Inhibition of the JAK/STAT pathway, as demonstrated with Ruxolitinib, presents a promising therapeutic strategy for managing SO2-related allergic inflammation.