Project Summary/Abstract We have developed innovative new approaches of administering immunotherapeutic enzymes that robustly directs immune cells away from chronic inflammation toward homeostasis through metabolic programming. Innovative fusion protein enzyme constructs in both tissue-anchored and circulating forms are investigated, quantifying cellular mechanisms of action in order to determine if different administration routes offer advantages. There is considerable need for new therapeutic options for the chronic auto-inflammatory disease, psoriasis, which irreversibly damage epidermal tissues.