Adipocyte adaptive immunity mediates diet-induced adipose inflammation and insulin resistance by decreasing adipose Treg cells
Adipocyte adaptive immunity mediates diet-induced adipose inflammation and insulin resistance by decreasing adipose Treg cells
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DOI：
10.1038/ncomms15725
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发表时间：
2017-07-12
影响因子：
16.6
通讯作者：
Hsueh WA
中科院分区：
文献类型：
--
作者：
Deng T;Liu J;Deng Y;Minze L;Xiao X;Wright V;Yu R;Li XC;Blaszczak A;Bergin S;DiSilvestro D;Judd R;Bradley D;Caligiuri M;Lyon CJ;Hsueh WA
肥胖导致脂肪组织中CD_4~+T细胞亚群的转换，其特征是产生干扰素γ的Th1细胞增加，抗炎调节T细胞(Treg)减少，从而损害全身胰岛素敏感性。目前尚不清楚是什么标志着这些变化。在此，我们证明了脂肪细胞MHCII的遗传缺陷降低了肥胖小鼠脂肪干扰素γ的表达，增加了脂肪Treg的丰度，从而在不影响体重增加的情况下减少了肥胖引起的脂肪炎症和胰岛素抵抗。高脂饮食喂养的脂肪细胞特异性MHCII基因敲除(aMHCII−/−)小鼠的胰岛素敏感性通过脂肪特异性Treg消融显著减弱。AMHCII−/−小鼠的脂肪细胞刺激Th1细胞产生干扰素γ的能力降低，而高脂饲料喂养的干扰素γR1−/−小鼠对胰岛素更敏感，脂肪组织中的Tregs水平与aMHCII−/−小鼠相似。我们进一步表明，干扰素γ强烈抑制IL-33促进脂肪Treg增殖的作用。我们的结果确认脂肪细胞中的MHCII是肥胖诱导的脂肪T细胞亚群转换和胰岛素抵抗的关键决定因素。肥胖与脂肪组织中的炎症有关，其特征是局部T细胞亚群的变化。在这里，作者表明，脂肪细胞上MHCII表达的缺失增加了脂肪组织中免疫抑制调节性T细胞的水平，从而增强了胰岛素敏感性。
Obesity leads to a switch in subsets of CD4+ T cell in adipose tissue, characterized by an increase in IFNγ producing Th1 cells and a decrease in anti-inflammatory regulatory T (Treg) cells, which impairs systemic insulin sensitivity. What signals these changes is unknown. Herein we demonstrate that genetic deficiency of adipocyte MHCII decreases adipose IFNγ expression and increases adipose Treg abundance in obese mice, leading to reduced obesity-induced adipose inflammation and reduced insulin resistance without affecting weight gain. The preserved insulin sensitivity of high fat diet (HFD)-fed adipocyte-specific MHCII knockout (aMHCII−/−) mice was substantially attenuated by adipose-specific Treg ablation. Adipocytes of aMHCII−/− mice exhibit decreased capacity to stimulate IFNγ production in Th1 cells, whereas HFD-fed IFNγR1−/− mice were more insulin sensitive and had similarly high levels of Tregs in adipose tissue as aMHCII−/− mice. We further show that IFNγ strongly inhibits IL-33 effects to promote adipose Treg proliferation. Our results identify MHCII in adipocyte as a critical determinant of the obesity-induced adipose T cell subset switch and insulin resistance. Obesity is associated with inflammation in adipose tissue, characterized by a shift in local T cell subsets. Here the authors show that loss of MHCII expression on adipocytes increases levels of immunosuppressive regulatory T cells in adipose tissue, which enhances insulin sensitivity.
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影响因子：
29
作者：
Deng T;Lyon CJ;Minze LJ;Lin J;Zou J;Liu JZ;Ren Y;Yin Z;Hamilton DJ;Reardon PR;Sherman V;Wang HY;Phillips KJ;Webb P;Wong ST;Wang RF;Hsueh WA
通讯作者：
Hsueh WA
DOI：
10.1073/pnas.80.1.273
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
MATHIS, DJ;BENOIST, C;MCDEVITT, HO
通讯作者：
MCDEVITT, HO
影响因子：
30.5
作者：
Liu, Xingguang;Zhan, Zhenzhen;Cao, Xuetao
通讯作者：
Cao, Xuetao
影响因子：
29
作者：
Kolodin D;van Panhuys N;Li C;Magnuson AM;Cipolletta D;Miller CM;Wagers A;Germain RN;Benoist C;Mathis D
通讯作者：
Mathis D
影响因子：
3.7
作者：
Deiuliis J;Shah Z;Shah N;Needleman B;Mikami D;Narula V;Perry K;Hazey J;Kampfrath T;Kollengode M;Sun Q;Satoskar AR;Lumeng C;Moffatt-Bruce S;Rajagopalan S
通讯作者：
Rajagopalan S