دورية أكاديمية

Obesity alters pathology and treatment response in inflammatory disease

التفاصيل البيبلوغرافية
العنوان: Obesity alters pathology and treatment response in inflammatory disease
المؤلفون: Bapat, Sagar P, Whitty, Caroline, Mowery, Cody T, Liang, Yuqiong, Yoo, Arum, Jiang, Zewen, Peters, Michael C, Zhang, Ling-juan, Vogel, Ian, Zhou, Carmen, Nguyen, Vinh Q, Li, Zhongmei, Chang, Christina, Zhu, Wandi S, Hastie, Annette T, He, Helen, Ren, Xin, Qiu, Wenli, Gayer, Sarah G, Liu, Chang, Choi, Eun Jung, Fassett, Marlys, Cohen, Jarish N, Sturgill, Jamie L, Crotty Alexander, Laura E, Suh, Jae Myoung, Liddle, Christopher, Atkins, Annette R, Yu, Ruth T, Downes, Michael, Liu, Sihao, Nikolajczyk, Barbara S, Lee, In-Kyu, Guttman-Yassky, Emma, Ansel, K Mark, Woodruff, Prescott G, Fahy, John V, Sheppard, Dean, Gallo, Richard L, Ye, Chun Jimmie, Evans, Ronald M, Zheng, Ye, Marson, Alexander
المصدر: Nature, vol 604, iss 7905
بيانات النشر: eScholarship, University of California
سنة النشر: 2022
المجموعة: University of California: eScholarship
مصطلحات موضوعية: Biomedical and Clinical Sciences, Immunology, Obesity, Prevention, Genetics, Nutrition, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Inflammatory and immune system, Stroke, Oral and gastrointestinal, Good Health and Well Being, Animals, Cytokines, Dermatitis, Atopic, Disease Models, Animal, Inflammation, Mice, PPAR gamma, Precision Medicine, Sequence Analysis, RNA, Th2 Cells, General Science & Technology
جغرافية الموضوع: 337 - 342
الوصف: Decades of work have elucidated cytokine signalling and transcriptional pathways that control T cell differentiation and haveled the way to targeted biologic therapies that are effective in a range of autoimmune, allergic and inflammatory diseases. Recent evidence indicates that obesity and metabolic disease can also influence the immune system1-7, although the mechanisms and effects on immunotherapy outcomes remain largely unknown. Here, using two models of atopic dermatitis, we show that lean and obese mice mount markedly different immune responses. Obesity converted the classical type 2 T helper (TH2)-predominant disease associated with atopic dermatitis to a more severe disease with prominent TH17 inflammation.We also observed divergent responses to biologic therapies targeting TH2 cytokines, which robustly protected lean mice but exacerbated disease in obese mice. Single-cell RNA sequencing coupled with genome-wide binding analyses revealed decreased activity of nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) in TH2 cells from obese mice relative to lean mice. Conditional ablation of PPARγ in T cells revealed that PPARγ is required to focus the in vivo TH response towards a TH2-predominant state and prevent aberrant non-TH2 inflammation. Treatment of obese mice with a small-molecule PPARγ agonist limited development of TH17 pathology and unlocked therapeutic responsiveness to targeted anti-TH2 biologic therapies. These studies reveal the effects of obesity on immunological disease and suggest a precision medicine approach to target the immune dysregulation caused by obesity.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: unknown
العلاقة: qt2bv4q0k3; https://escholarship.org/uc/item/2bv4q0k3Test
الإتاحة: https://escholarship.org/uc/item/2bv4q0k3Test
حقوق: public
رقم الانضمام: edsbas.BEDC6EA6
قاعدة البيانات: BASE