Leptin induces TNFα-dependent inflammation in acquired generalized lipodystrophy and combined Crohn’s disease
Leptin induces TNFα-dependent inflammation in acquired generalized lipodystrophy and combined Crohn’s disease
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瘦素在获得性全身性脂肪营养不良和合并克罗恩病中诱导 TNFα 依赖性炎症
DOI：
10.1038/s41467-019-13559-7
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发表时间：
2019
影响因子：
16.6
通讯作者：
Löscher
中科院分区：
文献类型：
--
作者：
Ziegler J;Boettcher C;Letizia M;Cansu Y;Freise I;Rodriguez-Sillke Y;Stoyanova A;Kreis M;Asbach P;Kunkel D;Priller J;Anagnostopoulos I;Kuehl A;Miehle K;Stumvoll M;Tran F;Fredrich B;Fordter M;Franke A;Bojarski C;Glauben R;Löscher
瘦素已被证明可以调节小鼠的肠道炎症。然而，关于其在人类克罗恩病中的免疫刺激潜力的临床证据仍然很少。我们在这里描述了一个病人的独特组合获得性全身性脂肪营养不良和克罗恩病（AGLCD）的特点是缺乏脂肪组织，瘦素缺乏症和肠道炎症。使用质量和流式细胞术，免疫组织化学和功能代谢分析，AGLCD患者进行了比较，健康人和克罗恩病患者的免疫细胞组成，功能和代谢和重组N-甲硫氨酰瘦素（rLeptin）的影响进行了评估。我们提供的证据表明，rLeptin对免疫细胞分化和功能发挥多种促炎作用，包括免疫细胞的代谢重编程和TNFα的诱导，最终加重AGLCD患者的克罗恩病，这可以通过抗TNF α治疗逆转。我们的研究结果表明，瘦素是人体免疫稳态所必需的，并以TNFα依赖的方式促进自身免疫。
Leptin has been shown to modulate intestinal inflammation in mice. However, clinical evidence regarding its immune-stimulatory potential in human Crohn’s disease remains sparse. We here describe a patient with the unique combination of acquired generalized lipodystrophy and Crohn’s disease (AGLCD) featuring a lack of adipose tissue, leptin deficiency and intestinal inflammation. Using mass and flow cytometry, immunohistochemistry and functional metabolic analyses, the AGLCD patient was compared to healthy individuals and Crohn’s disease patients regarding immune cell composition, function and metabolism and the effects of recombinantN-methionylleptin (rLeptin) were evaluated. We provide evidence that rLeptin exerts diverse pro-inflammatory effects on immune cell differentiation and function, including the metabolic reprogramming of immune cells and the induction of TNFα, ultimately aggravating Crohn’s disease in the AGLCD patient, which can be reversed by anti-TNFα therapy. Our results indicate that leptin is required for human immune homeostasis and contributes to autoimmunity in a TNFα-dependent manner.
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影响因子：
4
作者：
Greineisen WE;Speck M;Shimoda LM;Sung C;Phan N;Maaetoft-Udsen K;Stokes AJ;Turner H
通讯作者：
Turner H
影响因子：
15.9
作者：
Desvignes, Ludovic;Weidinger, Carl;Feske, Stefan
通讯作者：
Feske, Stefan
影响因子：
5.8
作者：
Oral, EA;Javor, ED;Gorden, P
通讯作者：
Gorden, P
影响因子：
5.8
作者：
Javor, ED;Moran, SA;Gorden, P
通讯作者：
Gorden, P
影响因子：
29
作者：
Chatterjee S;Daenthanasanmak A;Chakraborty P;Wyatt MW;Dhar P;Selvam SP;Fu J;Zhang J;Nguyen H;Kang I;Toth K;Al-Homrani M;Husain M;Beeson G;Ball L;Helke K;Husain S;Garrett-Mayer E;Hardiman G;Mehrotra M;Nishimura MI;Beeson CC;Bupp MG;Wu J;Ogretmen B;Paulos CM;Rathmell J;Yu XZ;Mehrotra S
通讯作者：
Mehrotra S