Targeted RNA Therapy Reprograms Fibrotic Macrophages to Reverse Pulmonary Fibrosis

Rationale: Pulmonary fibrosis is driven by maladaptive immune programs that reinforce fibroblast activation. We sought to determine whether profibrotic macrophage states could be therapeutically remodeled to alleviate fibrosis through targeted RNA-based modulation of their intrinsic regulatory circuitry. Methods: mRNA to assess macrophage state remodeling in fibrotic lungs. Results: mRNA transcriptionally redirected macrophages toward an inflammatory, antifibrotic state, resulting in attenuation of pulmonary fibrosis. Conclusions: These findings demonstrate that macrophage states can be therapeutically remodeled through targeted RNA-based modulation in pulmonary fibrosis. This strategy establishes state-level immune reprogramming as a potentially generalizable approach for dismantling pathogenic immune programs in fibrotic disease.