A key role of leptin in the control of regulatory T cell proliferation
A key role of leptin in the control of regulatory T cell proliferation
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DOI：
10.1016/j.immuni.2007.01.011
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发表时间：
2007-02-01
期刊：
影响因子：
32.4
通讯作者：
Matarese, Giuseppe
中科院分区：
文献类型：
--
作者：
De Rosa, Veronica;Procaccini, Claudio;Matarese, Giuseppe
我们在这里报告，瘦素可以作为一个负信号的人天然存在的Foxp 3（+）CD 4（+）CD 25（+）调节性T（T-reg）细胞的增殖。新鲜分离的Treg细胞产生瘦素并表达大量的瘦素受体（ObR）。在体外中和与瘦素单克隆抗体（mAb），在抗CD 3和抗CD 28刺激，导致T-reg细胞增殖，这是白细胞介素-2（IL-2）依赖性。在瘦素mAb存在下增殖的Treg细胞具有增加的Foxp 3表达并保持抑制。这种现象似乎继发于瘦素信号通过ObR，重要的是，瘦素中和逆转了Treg细胞的无反应性状态，如通过下调细胞周期蛋白依赖性激酶抑制剂p27（p27（kip 1））和细胞外相关激酶1（ERK 1）和ERK 2的磷酸化所示。连同在瘦素和ObR缺陷小鼠中观察到的T-reg细胞增殖增强的发现，这些结果表明免疫和自身免疫性疾病的治疗干预的潜力。
We report here that leptin can act as a negative signal for the proliferation of human naturally occurring Foxp3(+)CD4(+)CD25(+) regulatory T (T-reg) cells. Freshly isolated Treg cells produced leptin and expressed high amounts of leptin receptor (ObR). In vitro neutralization with leptin monoclonal antibody (mAb), during anti-CD3 and anti-CD28 stimulation, resulted in T-reg cell proliferation, which was interleukin-2 (IL-2) dependent. Treg cells that proliferated in the presence of leptin mAb had increased expression of Foxp3 and remained suppressive. The phenomena appeared secondary to leptin signaling via ObR and, importantly, leptin neutralization reversed the anergic state of the Treg cells, as indicated by downmodulation of the cyclin-dependent kinase inhibitor p27 (p27(kip1)) and the phosphorylation of the extracellular-related kinases 1 (ERK1) and ERK2. Together with the finding of enhanced proliferation of T-reg cells observed in leptin- and ObR-deficient mice, these results suggest a potential for therapeutic interventions in immune and autoimmune diseases.