IL-33-Responsive Group 2 Innate Lymphoid Cells Are Regulated by Female Sex Hormones in the Uterus.

IL-33-Responsive Group 2 Innate Lymphoid Cells Are Regulated by Female Sex Hormones in the Uterus.
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DOI:
10.4049/jimmunol.1602085
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发表时间:
2018-01-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Kita H
Kita H
中科院分区:
其他
文献类型:
--
作者:
Bartemes K;Chen CC;Iijima K;Drake L;Kita H

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第2组先天淋巴样细胞(ILC 2)存在于体内的多个器官中,在免疫、组织稳态和代谢调节中发挥作用。然而,对ILC 2在不同器官中的调节机制知之甚少。在这里,我们鉴定了小鼠子宫中的ILC 2,并发现它们表达细胞表面分子,包括IL-33受体ST 2,这些分子与肺ILC 2表达的分子大致相当。用IL-33在体内和体外处理均诱导子宫ILC 2中的2型细胞因子产生,这表明它们以与其他器官中的ILC 2类似的方式对IL-33作出反应。重要的是,子宫ILC 2在卵巢切除小鼠中几乎不存在,并且通过雌激素给药在野生型小鼠中增加,而肺ILC 2不受卵巢切除术和雌激素给药的影响。同样,在ERα或ERβ缺陷的小鼠中观察到子宫ILC 2显著减少。此外,子宫ILC 2s高表达雌激素受体α(ERα),并且在体外培养的分离的子宫ILC 2s与17β-雌二醇修饰了许多基因的表达。最后,在缺乏IL-33受体ST 2的母鼠的窝仔中观察到新生儿死亡率增加。总之,我们的研究结果表明,与肺IL 2Cs不同,子宫ILC 2受女性性激素的调节,这可能使其专门用于特定的生理功能。
Group 2 innate lymphoid cells (ILC2s) reside in multiple organs in the body, where they play roles in immunity, tissue homeostasis, and metabolic regulation. However, little is known about the regulatory mechanisms of ILC2s in different organs. Here, we identified ILC2s in the mouse uterus and found that they express cell surface molecules, including the IL-33 receptor ST2, that are roughly comparable to those expressed by lung ILC2s. Both in vivo and in vitro treatment with IL-33 induced type 2 cytokine production in uterine ILC2s, suggesting that they respond to IL-33 in a manner similar to ILC2s in other organs. Importantly, uterine ILC2s were nearly absent in ovariectomized mice and were increased in wild-type mice by estrogen administration, whereas lung ILC2s were unaffected by both ovariectomy and estrogen administration. Likewise, a marked reduction in uterine ILC2s was observed in mice deficient in ERα or ERβ. Furthermore, uterine ILC2s highly expressed estrogen receptor α (ERα), and in vitro culture of isolated uterine ILC2s with 17β-estradiol modified expression of a number of genes. Finally, an increased prevalence in neonatal mortality was observed in litters from dams lacking the IL-33 receptor, ST2. Taken together, our findings indicate that unlike lung IL2Cs, uterine ILC2s are regulated by female sex hormones, which may specialize them for specific physiological functions.
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