Engineered Photoactivatable Immune Modulators for Controlling Immunity

Macrophages and T helper 17 (Th17) cells, an important subset of CD4+ T cells, help to eliminate infectious pathogens that have invaded our tissues. Despite the critical roles of these cells in immunity, how the immune system regulates the production and maintenance of both cell types remains poorly understood. Here, we report a synthetic immunology approach using a photoactivatable immune modulator (PIM) to control the activities of these cells on demand with spatial and temporal precision to help elucidate their dynamic roles during the host immune response. In this chemical strategy, we developed a latent inhibitor/agonist that upon photochemical activation releases a small-molecule inhibitor or ligand that can inactivate or activate the respective cell type. We envision that this chemical approach will enable an understanding of the dynamic functions and behaviors of these immune cells in vivo during immune responses and in mouse models of inflammatory disease.