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Antigen-Specific mRNA–LNP Vaccination with mTOR Inhibition Promotes Treg Cells and Limits Allergy

ABSTRACT: Immune tolerance to T helper 2 (Th2)-mediated allergic reactions relies largely on antigen-specific T helper 1 (Th1) and regulatory T cells, which modulate downstream immune responses upon antigen exposure and mitigate allergic diseases. While allergen-encoded mRNA-lipid nanoparticle (mRNA-LNP) vaccine elicits Th1 and cytotoxic CD8+ T responses that counterbalance Th2 immunity, co-administration of mRNA-LNP with an mTOR inhibitor shifts this profile by promoting generation of functional regulatory T cells and partially attenuating Th1 and CD8+ T cell responses. In pre-clinical models of allergic asthma, this combinatorial strategy preserved the anti-allergic effects of mRNA-LNP immunization, reduced eosinophil activation markers, and limited vaccine-associated cytotoxicity. The ability of an mTOR inhibitor to profoundly modify mRNA-LNP vaccination by inducing regulatory T cells presents a potential strategy to enhance regulatory immunity in the treatment of allergy and other inflammatory diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE325304 | GEO | 2026/05/20

REPOSITORIES: GEO

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