Adoptive T _reg therapy with metabolic intervention via perforated microneedles ameliorates psoriasis syndrome

Abstract

Regulatory T (T reg ) cells underlie multiple autoimmune disorders and potentialize an anti-inflammation treatment with adoptive cell therapy. However, systemic delivery of cellular therapeutics often lacks tissue targeting and accumulation for localized autoimmune diseases. Besides, the instability and plasticity of T reg cells also induce phenotype transition and functional loss, impeding clinical translation. Here, we developed a perforated microneedle (PMN) with favorable mechanical performance and a spacious encapsulation cavity to support cell survival, as well as tunable channels to facilitate cell migration for local T reg therapy of psoriasis. In addition, the enzyme-degradable microneedle matrix could release fatty acid in the hyperinflammatory area of psoriasis, enhancing the T reg suppressive functions via the fatty acid oxidation (FAO)–mediated metabolic intervention. T reg cells administered through PMN substantially ameliorated psoriasis syndrome with the assistance of fatty acid–mediated metabolic intervention in a psoriasis mouse model. This tailorable PMN could offer a transformative platform for local cell therapy to treat a variety of diseases.