Immune regulation by mRNA: inducing antigen-specific Tregs for therapeutic applications 2211

Abstract Description We aimed to develop a safer approach to induce antigen-specific regulatory T cells (Tregs) in vivo for treating autoimmune diseases and allergies. Existing therapies, like immunosuppressive drugs, lack specificity and cause serious side effects. Tregs are key in maintaining immune tolerance and preventing autoimmune disease, but inducing antigen-specific Tregs in vivo remains challenging. We developed mRNA-X, encoding immune regulatory molecules along with antigens, to enhance Treg induction. Using the MOG antigen, a mouse model of multiple sclerosis, mRNA-X induced MOG-specific Tregs more efficiently than conventional mRNA and led to their accumulation in both the spleen and spinal cord. These Tregs expressed markers like CD25 and CTLA4 and reduced inflammatory cytokine release (IFN-γ, IL-2), showing improved safety over traditional methods. Moreover, mRNA-X prevented severe disease progression in an experimental autoimmune encephalomyelitis (EAE) model, whereas conventional MOG-mRNA did not. The successful induction of Tregs using another autoantigen and foreign antigens associated with autoimmune diseases and allergies indicates that mRNA-X has potential for use in both autoimmune and foreign antigen-associated diseases. Future studies will focus on assessing broader applicability and safety in human clinical trials. Funding Sources Japan Society for the Promotion of Science (JSPS)/DC2 202412638 (SI), The Japan Science and Technology Agency (JST) Precursory Research for Embryonic Science and Technology (PRESTO) (No. JPMJPR19HA to TY), JST Fusion Oriented Research for Disruptive Science and Technology (FOREST) grant no. JPMJFR2115 (TY) Topic Categories Therapeutic Approaches to Autoimmunity (THER)