GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328352/primaryOK200GenomicsHomo sapiensGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328352GEOGSEfalseEngineered Amphiregulin Promotes Tissue Healing via Dual Regenerative and Immunomodulatory Functions in Tissue-Resident Non-Immune CellsAmphiregulin (AREG), a growth factor expressed by immune cells, has emerged as an important mediator of tissue healing. However, its therapeutic potential and immunomodulatory effects remain elusive. Here, we engineered an optimized AREG (eAREG) with enhanced signaling and an ability to tissue retention. We show that eAREG promotes robust skin repair and muscle regeneration in murine models. Mechanistically, eAREG acts on tissue-resident non-immune cells to suppress inflammation-induced chemokines, thereby limiting the recruitment of pro-inflammatory immune cells. We further demonstrate that eAREG constrains chromatin accessibility at regulatory regions of key chemokine genes, revealing an epigenetic mechanism of immune regulation operating within non-immune tissue compartments. Importantly, the regenerative and immunomodulatory effects of eAREG are preserved in diabetic mice with elevated inflammation and impaired healing. Together, these findings identify eAREG as a dual-function regenerative biologic and establish a design principle for regenerative therapies that integrate morphogenic signaling with immunomodulation mediated by tissue-resident cells.2026/05/19GSE328352GSM9679762GSM9679761GSM9679760GSM9679755GSM9679754GSM9679764GSM9679753GSM9679763GSM9679759GSM9679758GSM9679757GSM967975630173328352Homo sapiens