GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE309nnn/GSE309156/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE309156GEOGSEfalseMannose-Modified Tobacco Mosaic Virus-Mediated Macrophage Regulation Inhibits Pulmonary Fibrosis ProgressionIdiopathic pulmonary fibrosis (IPF) is a chronic disease, causing irreversible lung scarring and respiratory failure. CD206+ M2 macrophages play a key role in its progression. In this study, we utilize the pro-inflammatory properties of plant viruses to develop a mannose-modified tobacco mosaic virus nanoparticle (TMV-OEG8-Man), which targets and reprograms profibrotic macrophages to inhibit IPF. TMV-OEG8-Man alters the CD206+ M2 macrophage phenotype in vitro, suppressing profibrotic genes (Mrc1, Spp1, Ccr2) and signaling pathways (MAPK, TGF-beta, PI3K-Akt, mTOR, Wnt), thereby reducing the transition of fibroblasts to myofibroblasts. When administered via aerosol, TMV-OEG8-Man achieves prolonged lung retention with minimal systemic exposure. In mice with bleomycin-induced pulmonary fibrosis, a single dose during fibroproliferation attenuated fibrosis progression, increasing survival rate from 50% to 100%, and preserving lung architecture. This study establishes plant viral nanoparticles as a macrophage reprogramming strategy with therapeutic potential for organ fibrosis.2026/07/29GSE309156GSM9262202GSM9262203GSM9262200GSM9262201GSM9262198GSM9262199GSM9262206GSM9262204GSM926220524247309156Mus musculus