Estradiol suppresses psoriatic inflammation in mice by regulating neutrophil and macrophage functions
Estradiol suppresses psoriatic inflammation in mice by regulating neutrophil and macrophage functions
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DOI：
10.1016/j.jaci.2022.03.028
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发表时间：
2022-10-04
影响因子：
14.2
通讯作者：
Kabashima, Kenji
中科院分区：
文献类型：
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作者：
Adachi, Akimasa;Honda, Tetsuya;Kabashima, Kenji
背景：银屑病是一种常见的炎症性皮肤病，由IL-23/T（H）17免疫轴失调引起。银屑病的患病率和严重程度在男性中高于女性，尽管其根本原因尚不清楚。目的：我们研究了雌激素雌二醇是否通过调节中性粒细胞和巨噬细胞的功能在咪喹莫特诱导的小鼠银屑病炎症中起保护作用目的：我们研究了雌激素雌二醇是否通过调节中性粒细胞和巨噬细胞的功能在咪喹莫特诱导的小鼠银屑病炎症中起保护作用。对野生型小鼠和条件性基因敲除小鼠进行卵巢切除，补充安慰剂或雌二醇颗粒，并涂抹含咪喹莫特的乳膏。没有内源性卵巢激素的小鼠表现出加重的银屑病炎症，包括IL-17 A和IL-1 β的产生增加，这被外源性添加的雌二醇逆转。在中性粒细胞和巨噬细胞中缺乏雌激素受体的小鼠（Esr 1（f/f）Esr 2（f/f）LysM-Cre+小鼠）中，雌二醇对IL-1 β和IL-17 A产生的抑制作用消失。在银屑病模型中产生IL-17 A所需的IL-1 β主要由嗜中性粒细胞和炎性巨噬细胞产生。雌二醇抑制白细胞介素-1 β的产生从中性粒细胞和巨噬细胞在小鼠体内和体外，从人类中性粒细胞在vitro.Conclusion：我们的研究结果表明，银屑病的临床表型，可能揭示了新的光银屑病的病理性别依赖性差异的一种新的机制。
Background: Psoriasis is a common inflammatory skin disease resulting from dysregulation of the IL-23/T(H)17 immune axis. The prevalence and severity of psoriasis is higher in men than in women, although the underlying reasons for this are unclear. Objective: We studied whether estradiol, a female hormone, plays protective roles in imiquimod-induced psoriatic inflammation in mice by regulating neutrophil and macrophage functions.Objective: We studied whether estradiol, a female hormone, plays protective roles in imiquimod-induced psoriatic inflammation in mice by regulating neutrophil and macrophage functions.Methods: Wild-type mice and conditional knockout mice were ovariectomized, supplemented with placebo or estradiol pellets, and an imiquimod-containing cream applied.Results: Mice without endogenous ovarian hormones exhibited exacerbated psoriatic inflammation including increased production of IL-17A and IL-1 beta, which was reversed by exogenously added estradiol. The suppressive effect of estradiol on the production of IL-1 beta and IL-17A was abolished in mice lacking estrogen receptors in neutrophils and macrophages (Esr1(f/f)Esr2(f/f)LysM-Cre+ mice). IL-1 beta, which is required for production of IL-17A in the psoriasis model, was mainly produced by neutrophils and inflammatory macrophages. Estradiol suppressed IL-1 beta production from neutrophils and macrophages in mice both in vivo and in vitro and from human neutrophils in vitro.Conclusion: Our results suggest a novel mechanism for sex-dependent differences in psoriasis clinical phenotypes that may shed new light on the pathology of psoriasis.