Metabolic Reprogramming of Immune for Autoimmune Disorders Prevention/Reversal

Antigen-specific immune suppression or tolerance is a highly attractive strategy to prevent inflammation-induced tissue damage in rheumatoid arthritis (RA). Although there is insufficient knowledge about autoantigens in human RA, generating and expanding synovium-specific regulatory T cells, and suppressing synovium-specific follicular T-helper cells, can provide global tissue-specific immunosuppression. Previous data suggests that tolerogenic dendritic cells can be generated using glycolytic inhibitors, and these are capable of generating antigen-specific regulatory T-cells in vivo. Thus, there is a need to develop technologies that can generate tissue-specific tolerance by targeting glycolysis pathways of immune cells, while providing multiple tissue antigens, without modulating systemic metabolism.

 

Researchers at Arizona State University developed a method and composition using polymeric microparticles encapsulating PFK15, a glycolytic inhibitor, aimed at modulating immune responses. By targeting dendritic cells with controlled delivery of PFK15, encapsulated within α-ketoglutarate polymer, it aims to inhibit glycolysis, suppress pro-inflammatory responses, and promote anti-inflammatory phenotypes, with a focus on autoimmune conditions like rheumatoid arthritis.

 

Potential Applications

Benefits and Advantages

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