肥胖会改变炎症疾病的病理和治疗反应
Sagar P Bapat1,2,3,4,5,6, Caroline Whitty7,8, Cody T Mowery8,9,10
1NOMIS Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA, USA. sagar.bapat@ucsf.edu.
Nature
|March 31, 2022
概括
肥胖会改变阿托皮性皮肤炎的免疫反应,使炎症从T助手2 (TH2) 转移到T助手17 (TH17) 细胞. 在T细胞中的PPARγ激活是预防肥胖引起的免疫失调的关键.
科学领域:
- 免疫学
- 代谢疾病研究
- 皮肤病学
背景情况:
- 细胞因子信号传递和T细胞分化对于免疫反应和向治疗至关重要.
- 肥胖和代谢疾病越来越多地影响免疫系统,但机制尚不清楚.
- 肥胖对免疫治疗结果的影响在很大程度上是未知的.
研究的目的:
- 研究肥胖如何影响亚托皮炎模型中的免疫反应.
- 确定肥胖引起的免疫失调的机制.
- 探索与肥胖相关的炎症疾病的治疗策略.
主要方法:
- 在瘦身和肥胖小鼠中使用了两种类型的亚托皮炎.
- 进行单细胞RNA测序和全基因组结合分析.
- 在T细胞中进行过氧酶增殖器激活受体-γ (PPARγ) 的条件切除.
- 给肥胖小鼠使用小分子PPARγ激应剂.
主要成果:
- 肥胖症使皮炎从TH2占主导地位转变为严重的TH17炎症.
- 针对TH2细胞因子的生物疗法在瘦小鼠中有效,但在肥胖小鼠中恶化了疾病.
- 肥胖小鼠在TH2细胞中的PPARγ活性下降,而PPARγ对于TH2主导反应至关重要.
- 在肥胖小鼠中,PPARγ激动剂治疗减少了TH17病理,并恢复了对抗TH2疗法的反应.
结论:
- 肥胖会显著改变亚托皮炎的免疫反应,导致更严重的TH17驱动的炎症.
- 在维持TH2集中免疫反应和预防异常炎症方面,PPARγ起着至关重要的作用.
- 针对PPARγ提供了一种潜在的精准医学方法来管理因肥胖引起的免疫失调并改善治疗结果.
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