Adoptive T <sub>reg</sub> therapy with metabolic intervention via perforated microneedles ameliorates psoriasis syndrome
Wentao Zhang, Yingxin Chen, Zhengjie Zhao, Hanqi Zheng, Shenqiang Wang, Ziyan Liao, Tao Sheng, Sheng Zhao, Wenhui Hou, Xinmin Yu, Fang He, Jicheng Yu, Yuqi Zhang, Zhen Gu
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.