Engineering synthetic suppressor T cells that execute locally targeted immunoprotective programs.

ABSTRACT: Immune homeostasis requires a balance of inflammatory and suppressive activities. To design cells potentially useful for local immune suppression, we engineered conventional CD4⁺ T cells with synthetic Notch (synNotch) receptors driving antigen-triggered production of anti-inflammatory payloads. Screening a diverse library of suppression programs, we observed the strongest suppression of cytotoxic T cell attack by the production of both anti-inflammatory factors (interleukin-10, transforming growth factor-β1, programmed death ligand 1) and sinks for proinflammatory cytokines (interleukin-2 receptor subunit CD25). Engineered cells with bespoke regulatory programs protected tissues from immune attack without systemic suppression. Synthetic suppressor T cells protected transplanted

SUBMITTER: Reddy NR 

PROVIDER: S-EPMC11831968 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature