Erratum: The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue-resident regulatory T cells.
Erratum: The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue-resident regulatory T cells.
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勘误表：转录调节因子 IRF4、BATF 和 IL-33 协调脂肪组织驻留调节性 T 细胞的发育和维持。
DOI：
10.1038/ni0515-544d
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发表时间：
2015
影响因子：
30.5
通讯作者：
Leonard
中科院分区：
文献类型：
--
作者：
Vasanthakumar,Ajithkumar;Moro,Kazuyo;Xin,Annie;Liao,Yang;Gloury,Renee;Kawamoto,Shimpei;Fagarasan,Sidonia;Mielke,LisaA;Afshar-Sterle,Shoukat;Masters,SethL;Nakae,Susumu;Saito,Hirohisa;Wentworth,JohnM;Li,Peng;Liao,Wei;Leonard
内脏脂肪组织中的Foxp 3+调节性T（Treg）细胞（VAT-Tregcells）是功能特化的组织驻留细胞，其防止肥胖相关的炎症并保持胰岛素敏感性和葡萄糖耐受性。它们的发育依赖于转录因子PPAR-γ;然而，它们分化所需的环境因素尚不清楚。在这里，我们表明，白细胞介素33（IL-33）信号通过IL-33受体ST 2和髓样分化因子MyD 88是必不可少的发展和维持VAT-Treg细胞，并维持其转录签名。此外，转录调控因子BATF和IRF 4通过直接调控ST 2和PPAR-γ的表达，是VAT-Treg分化所必需的。IL-33给药诱导VAT-Treg细胞的剧烈群体扩增，这与肥胖小鼠代谢参数的改善密切相关。人网膜脂肪组织Treg细胞也显示出高ST 2表达，表明在VAT-Treg细胞稳态中对IL-33的进化保守需求。
Foxp3+regulatory T (Treg) cells in visceral adipose tissue (VAT-Tregcells) are functionally specialized tissue-resident cells that prevent obesity-associated inflammation and preserve insulin sensitivity and glucose tolerance. Their development depends on the transcription factor PPAR-γ; however, the environmental cues required for their differentiation are unknown. Here we show that interleukin 33 (IL-33) signaling through the IL-33 receptor ST2 and myeloid differentiation factor MyD88 is essential for development and maintenance of VAT-Tregcells and sustains their transcriptional signature. Furthermore, the transcriptional regulators BATF and IRF4 were necessary for VAT-Tregdifferentiation through direct regulation of ST2 and PPAR-γ expression. IL-33 administration induced vigorous population expansion of VAT-Tregcells, which tightly correlated with improvements in metabolic parameters in obese mice. Human omental adipose tissue Tregcells also showed high ST2 expression, suggesting an evolutionarily conserved requirement for IL-33 in VAT-Tregcell homeostasis.