Estrogen protects both sexes against EAE by promoting common regulatory cell subtypes independent of endogenous estrogen.

Estrogen protects both sexes against EAE by promoting common regulatory cell subtypes independent of endogenous estrogen.
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DOI:
10.1007/s11011-017-0063-8
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发表时间:
2017-10
影响因子:
3.6
通讯作者:
Offner H
Offner H
中科院分区:
医学3区
文献类型:
--
作者:
Seifert HA;Benedek G;Nguyen H;Kent G;Vandenbark AA;Offner H

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包括多发性硬化症在内的自身免疫性疾病主要影响女性。虽然高水平的性激素,特别是雌激素(E2)可以降低促炎免疫反应,但尚不清楚内源性激素的缺乏是否会影响外源性性激素的治疗。雌二醇预处理通过促进多种免疫细胞表型,几乎完全阻止正常雌性和雄性小鼠出现实验性自身免疫性脑脊髓炎(EAE)的临床和组织学体征。为了评价在缺乏内源性性激素的情况下外源性雌激素的作用,本研究比较了去卵巢(OVX)雌性和雄性小鼠EAE的严重程度和E2预处理后不同免疫调节细胞群的出现情况。我们发现,在21天的观察期内,雌雄两种动物对EAE的保护作用是相同的,同时伴随着脾和脊髓(仅雄性)细胞总数的减少,但两组CD19+CD5+CD1dhi、CD19+CD138+CD44hi和CD19+Tim-1+Breg细胞、CD8+CD122+Treg细胞和CD11b+206+Arg-1+抗炎M2样单核/巨噬细胞的百分率均升高。相反,雌激素E2降低了雌性去卵巢小鼠的CD4+CD25+FoxP3+Treg细胞的百分比,但增加了雄性和正常雌性小鼠的这些Treg细胞。这些数据表明,除了CD4+CD25+FoxP3+Treg细胞外,E2对EAE的保护促进了OVX女性和男性高度重叠的免疫调节亚群。
Autoimmune diseases including multiple sclerosis predominantly affect females. Although high levels of sex hormones, particularly estrogen (E2), can reduce proinflammatory immune responses, it remains unclear if a lack of endogenous sex hormones might affect treatment with exogenous sex hormones. Pretreatment with E2 almost completely prevents intact female and male mice from developing clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) by promoting various regulatory immune cell phenotypes. To evaluate the effects of exogenous estrogen in the absence of endogenous sex hormones, the current study compared EAE severity and the emergence of different immunoregulatory cell populations after E2 pretreatment of ovariectomized (OVX) female versus male mice. We found that E2 equally protected both OVX females and males from EAE over a 21 day observation period concomitant with reduced total cell numbers in spleen and spinal cord (males only), but enhanced percentages of CD19+CD5+CD1dhi, CD19+CD138+CD44hi and CD19+Tim-1+ Breg cells, CD8+CD122+ Treg cells and CD11b+206+ARG-1+ anti-inflammatory M2-like monocytes/macrophages in both groups. In contrast, E2 decreased the percentage of CD4+CD25+FoxP3+ Treg cells in OVX females but increased these Treg cells in males and intact female mice. These data suggest that with the exception of CD4+CD25+FoxP3+ Treg cells, E2 protection against EAE promotes highly overlapping immunoregulatory subsets in OVX females and males.
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