纤维母细胞网状细胞中的雌激素信号在抗原诱导的关节炎中对先天性和适应性免疫反应的作用

IF 3.2 4区 医学 Q3 CELL BIOLOGY Immunology & Cell Biology Pub Date : 2024-05-10 DOI:10.1111/imcb.12773
Aidan Barrett, Karin Horkeby, Carmen Corciulo, Hans Carlsten, Marie K Lagerquist, Julia M Scheffler, Ulrika Islander
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引用次数: 0

摘要

女性更容易罹患类风湿性关节炎,发病高峰出现在更年期前后。雌激素对免疫系统有重大影响,对关节炎有保护作用。我们之前已经证明,用雌激素治疗可抑制小鼠关节炎模型中的炎症和关节破坏,但其中的机制仍不清楚。成纤维网状细胞(FRCs)是一种特化的基质细胞,可形成淋巴结(LNs)的三维结构。成纤维网状细胞对协调淋巴结内的免疫反应至关重要,其特点是表达趋化因子 CCL19,这种趋化因子能吸引免疫细胞。本研究旨在确定雌激素对关节炎中先天性和适应性免疫细胞的影响是否由 FRCs 中的雌激素信号传导介导。本研究生成并测试了表达 CCL19 的细胞中缺乏雌激素受体α(ERα)的条件性基因敲除小鼠(Ccl19-CreERαfl/fl)。对Ccl19-CreERαfl/fl小鼠和同窝对照小鼠进行卵巢切除,用药物或雌二醇治疗,并进行长达28天的抗原诱导关节炎模型试验,以便通过流式细胞术分析LN中分化的T细胞和B细胞群以及先天性细胞。研究结果表明,虽然在FRCs中缺乏ERα的小鼠中,每个LN的FRCs数量对雌二醇治疗的反应明显降低,但在这种关节炎模型中,雌激素并不能抑制关节炎症或明显影响免疫反应。因此,本研究验证了 Ccl19-CreERαfl/fl 株在研究炎症性疾病中 FRCs 的雌激素信号转导时的有效性,尽管所选的关节炎模型不适合解决这一问题。
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Role of estrogen signaling in fibroblastic reticular cells for innate and adaptive immune responses in antigen-induced arthritis

Women are more prone to develop rheumatoid arthritis, with peak incidence occurring around menopause. Estrogen has major effects on the immune system and is protective against arthritis. We have previously shown that treatment with estrogen inhibits inflammation and joint destruction in murine models of arthritis, although the mechanisms involved remain unclear. Fibroblastic reticular cells (FRCs) are specialized stromal cells that generate the three-dimensional structure of lymph nodes (LNs). FRCs are vital for coordinating immune responses from within LNs and are characterized by the expression of the chemokine CCL19, which attracts immune cells. The aim of this study was to determine whether the influence of estrogen on innate and adaptive immune cells in arthritis is mediated by estrogen signaling in FRCs. Conditional knockout mice lacking estrogen receptor α (ERα) in CCL19-expressing cells (Ccl19-CreERαfl/fl) were generated and tested. Ccl19-CreERαfl/fl mice and littermate controls were ovariectomized, treated with vehicle or estradiol and subjected to the 28-day-long antigen-induced arthritis model to enable analyses of differentiated T- and B-cell populations and innate cells in LNs by flow cytometry. The results reveal that while the response to estradiol treatment in numbers of FRCs per LN is significantly reduced in mice lacking ERα in FRCs, estrogen does not inhibit joint inflammation or markedly affect immune responses in this arthritis model. Thus, this study validates the Ccl19-CreERαfl/fl strain for studying estrogen signaling in FRCs within inflammatory diseases, although the chosen arthritis model is deemed unsuitable for addressing this question.

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来源期刊
Immunology & Cell Biology
Immunology & Cell Biology 医学-免疫学
CiteScore
7.50
自引率
2.50%
发文量
98
审稿时长
4-8 weeks
期刊介绍: The Australasian Society for Immunology Incorporated (ASI) was created by the amalgamation in 1991 of the Australian Society for Immunology, formed in 1970, and the New Zealand Society for Immunology, formed in 1975. The aim of the Society is to encourage and support the discipline of immunology in the Australasian region. It is a broadly based Society, embracing clinical and experimental, cellular and molecular immunology in humans and animals. The Society provides a network for the exchange of information and for collaboration within Australia, New Zealand and overseas. ASI members have been prominent in advancing biological and medical research worldwide. We seek to encourage the study of immunology in Australia and New Zealand and are active in introducing young scientists to the discipline.
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