AHR-Responsive Carbon Dots Orchestrate Skin Wound Healing and Colonic Mucosal Repair via Treg-Mediated Macrophage Efferocytosis.

As critical interface organs, the gut and skin share substantial immunological similarities, and gut diseases are often accompanied by skin comorbidities, yet the underlying mechanisms remain unclear. Here, we observed delayed skin wound healing in a mouse model of colitis. To promote both skin and intestinal repair, we designed aryl hydrocarbon receptor (AHR)-responsive carbon dots using pharmacophore modeling and fragment-based drug design. These nanoscale carbon dots significantly alleviated colitis and accelerated impaired skin wound healing. The carbon dots preferentially accumulated in the inflamed colon, where they induced infiltration of tissue-resident regulatory T (Treg) cells, thereby suppressing mucosal inflammation and promoting tissue repair. Mechanistically, the carbon dots activated AHR signaling to drive Treg cell differentiation. Importantly, Treg-derived chemokine CCL1 enhanced macrophage efferocytosis, establishing a pro-regenerative immune microenvironment in both the colon and skin wounds via STAT3-SCARB1 signaling. Notably, Ccl1 knockdown attenuated the therapeutic effects of carbon dots on both colonic mucosal repair and skin wound healing, supporting CCL1 as a key mediator of gut-skin immune communication. Collectively, this study highlights the important role of Treg cells in gut-skin axis crosstalk and provides a nanomaterial-based strategy for coordinated tissue repair.