This talk will discuss immune modulation as a strategy for repairing the skin after a severe UV sunburn. Our group has had a long interest in investigating treatments to repair the skin following injury from sunburns and from exposures to toxic chemicals and radiation. We have shown that high dose oral vitamin D3 mitigates inflammation from experimental UV-induced sunburns in randomized double-blinded placebo-controlled human clinical studies. Subjects receiving vitamin D3 had reduced expression of pro-inflammatory mediators TNFa and iNOS in the skin 48 hours after a sunburn. Clustering subjects based on global gene expression profiles shows that those with higher serum vitamin D3 levels after intervention had increased skin expression of arginase-1 (Arg-1), a pro-resolution gene expressed by reparative macrophages. Modeling these studies in animal models, we have shown that skin recovery from sunburns is mediated by the action of anti-inflammatory M2 macrophages to promote epidermal regeneration. Furthermore, we demonstrate that vitamin D enhances macrophage autophagy and polarization towards the M2 repair phenotype. Pharmacological inhibition of autophagy increased UV-induced apoptosis and inhibited M2 recruitment into the skin resulting in severe skin damage. More recently, we demonstrate that a novel topical synthetic melanin working as a potent ROS scavenger augments the skin microenvironment facilitating recruitment of reparative TGF-b+/IL-10+ monocytes and M2-macrophages to heal the skin.