A Stat6/Pten Axis Links Regulatory T Cells with Adipose Tissue Function.
A Stat6/Pten Axis Links Regulatory T Cells with Adipose Tissue Function.
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DOI：
10.1016/j.cmet.2017.08.008
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发表时间：
2017-09-05
期刊：
影响因子：
29
通讯作者：
Daniel C
中科院分区：
文献类型：
--
作者：
Kälin S;Becker M;Ott VB;Serr I;Hosp F;Mollah MMH;Keipert S;Lamp D;Rohner-Jeanrenaud F;Flynn VK;Scherm MG;Nascimento LFR;Gerlach K;Popp V;Dietzen S;Bopp T;Krishnamurthy P;Kaplan MH;Serrano M;Woods SC;Tripal P;Palmisano R;Jastroch M;Blüher M;Wolfrum C;Weigmann B;Ziegler AG;Mann M;Tschöp MH;Daniel C
Obesity and type-2 diabetes are associated with tissue-inflammation and metabolic defects in fat depots. Foxp3+regulatory T(Treg) cells mediate T-cell tolerance, thereby controlling tissue inflammation. However, the molecular underpinnings how environmental stimuli interlink T-cell tolerance with adipose tissue function remain largely unknown. Here, we report that cold exposure or beta3-adrenergic receptor (ADRB3) stimulation induces T-cell tolerance in vitro and in murine and humanized models. Tolerance induction was verified by CD4+T-cell-proteomes revealing higher protein expression of Foxp3 regulatory networks. Specifically, Ragulator-interacting protein C17orf59, which limits mTORC1 activity, was upregulated by either ADRB3-stimulation or cold-exposure, and therefore might enhance Treg induction. By loss and gain-of-function studies, including Treg depletion and transfers in vivo, we demonstrated that a T-cell-specific Stat6/Pten axis links cold-exposure or ADRB3 stimulation with Foxp3+Treg induction and adipose tissue function. Our findings open new avenues in understanding tissue-specific T-cell tolerance and the design of precision concepts toward personalized immune-metabolic health. Inflammatory processes in metabolically active tissues are believed to contribute to the development of obesity and type-2 diabetes. We here report that immunesuppressive regulatory T cells represent key components of the molecular interface connecting environmental influences with functional integrity of adipose tissue in mice and men. Specifically, we find that a T cell-specific Stat6/Pten signaling axis links cold exposure or adrenergic stimuli with regulatory T cell activity and adipose tissue function, offering novel molecular approaches toward personalized immune-metabolic health.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
30.5
作者：
Chang CH;Pearce EL
通讯作者：
Pearce EL
影响因子：
64.5
作者：
Fedorenko A;Lishko PV;Kirichok Y
通讯作者：
Kirichok Y
影响因子：
4.4
作者：
Cox, Juergen;Neuhauser, Nadin;Mann, Matthias
通讯作者：
Mann, Matthias
通过强烈的激动剂胰岛素模拟蛋白的耐受性疫苗接种，预防小鼠中1型糖尿病。
DOI：
10.1084/jem.20110574
发表时间：
2011-07-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Daniel C;Weigmann B;Bronson R;von Boehmer H
通讯作者：
von Boehmer H