Abstract: This disclosure provides, among other things, an engineered immunosuppressive (e.g., CD4+) T cell comprising a molecular circuit comprising the following components: (a) a central nervous system (CNS)-specific binding-triggered transcriptional switch (BTTS); and (b) a nucleic acid encoding an anti-inflammatory payload, wherein binding of the BTTS to a marker on the surface of a target cell activates expression of the anti-inflammatory payload by the cell. A method of reducing inflammation in the brain of a subject is also provided.

Abstract: Provided herein is a synthetic immuno-suppressive cell that contains comprises a molecular circuit comprising the following components: (a) a binding-triggered transcriptional switch (BTTS); and one or both of: (b) a nucleic acid encoding a pro-inflammatory cytokine sink, (c) a nucleic acid encoding an anti-inflammatory cytokine, (d) a nucleic acid encoding an immune inhibitory receptor, or ligand thereof, and (c) a nucleic acid encoding an ectonucleotidase. In this circuit, binding of the BTTS to a marker on the surface of a target cell activates expression of one or any combination of (b)-(c) by the synthetic immuno-suppressive cell.