Adoptive T<sub>reg</sub> therapy with metabolic intervention via perforated microneedles ameliorates psoriasis syndrome.

Zhang, Wentao; Chen, Yingxin; Zhao, Zhengjie; Zheng, Hanqi; Wang, Shenqiang; Liao, Ziyan; Sheng, Tao; Zhao, Sheng et al. · Sci Adv · 2023

basic_science · Level V

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Abstract

Regulatory T (T<sub>reg</sub>) 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<sub>reg</sub> 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<sub>reg</sub> therapy of psoriasis. In addition, the enzyme-degradable microneedle matrix could release fatty acid in the hyperinflammatory area of psoriasis, enhancing the T<sub>reg</sub> suppressive functions via the fatty acid oxidation (FAO)-mediated metabolic intervention. T<sub>reg</sub> 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.

Medical subject headings