Ccl12 coordinates immune-neural crosstalk to promote adipose sympathetic remodeling after burn trauma.

Burn injury triggers sustained white adipose tissue (WAT) remodeling and hypermetabolism. While systemic catecholamines are considered primary drivers of this response, local mechanisms remain poorly defined. Here, we identify an intra-fat immune-neural axis that drives sympathetic remodeling and thermogenic reprogramming of WAT after burn. Using a murine scald model, we show that burn injury induces localized sympathetic activation, norepinephrine release, and WAT browning, all abolished by chemical or genetic denervation. Mechanistically, macrophage-derived Ccl12 recruits CCR2+ T cells that secrete nerve growth factor, promoting sympathetic neurite outgrowth and increasing intra-fat adrenergic tone. Disruption of this pathway through Ccl12 neutralization or T cell deficiency impairs WAT browning. Parallel features are observed in patients with burn injury, including increased sympathetic innervation, elevated uncoupling protein-1 expression, and enrichment of CCR2+ T cells in WAT. These findings reveal neural regulation of adipose function after burn and suggest potential targets for modulating hypermetabolism.