小柯机器人

美国埃默里大学医学院李超然研究组揭示，肥胖诱导的皮肤常驻过氧化物酶体增殖激活受体γ (PPARγ)+ 调节性T (Treg)细胞失调，促进IL-17A介导的银屑病炎症。相关论文于2023年7月20日发表于国际顶尖学术期刊《免疫》。

他们发现皮肤富含独特的CD4+Foxp3+表达核受体PPARγ的Treg细胞群。PPARγ驱动IL-17A+ γδ T细胞介导的银屑病炎症的独特转录程序和功能抑制。然而，饮食诱导的肥胖导致PPARγ+皮肤Treg细胞减少，并相应失去对IL-17A+ γδ T细胞介导的炎症的控制。在机制上，PPARγ+皮肤Treg细胞在肥胖小鼠中优先吸收高水平的长链游离脂肪酸，从而导致细胞脂毒性、氧化应激和线粒体功能障碍。利用这些PPARγ+皮肤Treg细胞的抗炎特性可能具有治疗肥胖相关炎症性皮肤病的潜力。

据了解，肥胖是牛皮癣的主要危险因素，但肥胖如何破坏控制皮肤炎症的调节机制尚不清楚。

附：英文原文

Title: Obesity-induced dysregulation of skin-resident PPARγ+ Treg cells promotes IL-17A-mediated psoriatic inflammation

Author: Pulavendran Sivasami, Cody Elkins, Pamela P. Diaz-Saldana, Kyndal Goss, Amy Peng, Michael Hamersky, Jennifer Bae, Miaoer Xu, Brian P. Pollack, Edwin M. Horwitz, Christopher D. Scharer, Lindsey Seldin, Chaoran Li

Issue&Volume: 2023-07-20

Abstract: Obesity is a major risk factor for psoriasis, but how obesity disrupts the regulatorymechanisms that keep skin inflammation in check is unclear. Here, we found that skinwas enriched with a unique population of CD4+Foxp3+ regulatory T (Treg) cells expressing the nuclear receptor peroxisome proliferation-activatedreceptor gamma (PPARγ). PPARγ drove a distinctive transcriptional program and functionalsuppression of IL-17A+ γδ T cell-mediated psoriatic inflammation. Diet-induced obesity, however, resultedin a reduction of PPARγ+ skin Treg cells and a corresponding loss of control over IL-17A+ γδ T cell-mediated inflammation. Mechanistically, PPARγ+ skin Treg cells preferentially took up elevated levels of long-chain free fatty acidsin obese mice, which led to cellular lipotoxicity, oxidative stress, and mitochondrialdysfunction. Harnessing the anti-inflammatory properties of these PPARγ+ skin Treg cells could have therapeutic potential for obesity-associated inflammatoryskin diseases.

DOI: 10.1016/j.immuni.2023.06.021

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00278-9

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