Restoration of IFN‐γ‐Producing MAIT Cell Correlates to Beneficial Allergen Immunotherapy in Allergic Rhinitis Patients

BACKGROUND: Mucosal-associated invariant T cells (MAIT) are emerging as important regulators at mucosal surfaces. While these cells have been linked to a Th1-biased immune response and support for B cells, their roles in allergic diseases characterised by type 2 inflammation remain elusive. The study seeks to characterise MAIT cells in house dust mite (HDM)-induced allergic rhinitis (AR) and subsequent allergen immunotherapy (AIT), aiming to elucidate their clinical significance in AR and potential to enhance AIT effectiveness. METHODS: MAIT cells were assessed in patients with AR and individuals undergoing AIT. The ratio and cytokine-producing capacity of these cells were analysed to explore their correlations with AR progression and their responsiveness to HDM extracts and MAIT cell-specific agonists. RESULTS: In AR patients, there was an increase in the ratios of circulating MAIT cells and tonsil follicular T helper-like MAIT cells, alongside a decrease in the IFN-γ-producing MAIT cells. AIT restored their IFN-γ producing capacity, which was further boosted by T cell receptor (TCR) activation using MAIT cell-specific agonist-loaded artificial antigen-presenting cells (aAPCs). Synergistic effects of aAPCs and HDM enhance MAIT cell activation and IFN-γ production while reducing HDM-induced IgE levels in PBMC cocultures. Moreover, higher ratios of MAIT cells and IFN-γ-producing MAIT cells correlated with decreased IgE and increased IgG4 and improved clinical outcomes during AIT. CONCLUSIONS: These findings underscore the compromised IFN-γ-producing MAIT cells in AR and their restoration following AIT and TCR stimulation, highlighting the cell's therapeutic potential and predictive value for clinical outcomes in AR and AIT.