IGF-1R在眼眶成纤维细胞和B淋巴细胞相互作用中的潜在作用:甲状腺相关性眼病活动性炎症阶段B淋巴细胞耗竭的含义。

IF 2.9 4区 医学 Q3 IMMUNOLOGY
Renyan Wang, Delu Song, Yong Zhong, Hui Li
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引用次数: 0

摘要

背景:甲状腺眼病(TED)是一种涉及淋巴细胞介导的免疫反应和眼眶组织损伤的炎症过程。B 淋巴细胞产生的抗胰岛素样生长因子-1 受体(IGF-1R)抗体参与了眼眶成纤维细胞的活化和 TED 眼眶组织损伤的炎症过程。本研究的目的是探讨IGF-1R在TED眼眶成纤维细胞与B淋巴细胞之间的机理联系中的作用:从15名TED患者和15名对照组患者的眼眶结缔组织中提取的眼眶成纤维细胞和从外周血中分离的外周B淋巴细胞按1:20的比例共同培养。流式细胞术和共聚焦显微镜评估了眼眶成纤维细胞中 IGF-1R 的表达水平。用抗CD20单克隆抗体利妥昔单抗诱导瞬时B淋巴细胞耗竭,同时用IGF-1R结合蛋白阻断IGF-1R通路。通过酶联免疫吸附测定了共培养模型中白细胞介素-6(IL-6)和正常T细胞表达和分泌的白细胞介素-6(RANTES)的表达水平:结果:与对照组相比,TED眼眶成纤维细胞的IGF-1R表达明显升高。眼眶成纤维细胞与外周B淋巴细胞共培养24小时后,各组(TED患者和对照组)的IL-6和RANTES表达水平均升高,其中TED患者(T + T组)的表达水平最高。利妥昔单抗和IGF-1R结合蛋白能显著抑制TED患者共培养模型中IL-6和RANTES水平的升高:结论:IGF-1R可能介导眼眶成纤维细胞与外周B淋巴细胞之间的相互作用;因此,阻断IGF-1R可减轻TED的局部炎症反应。利妥昔单抗介导的B淋巴细胞耗竭在该体外共培养模型中起到了抑制炎症反应的作用,为抗CD20单克隆抗体在TED中的临床应用提供了理论依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Potential role of IGF-1R in the interaction between orbital fibroblasts and B lymphocytes: an implication for B lymphocyte depletion in the active inflammatory phase of thyroid-associated ophthalmopathy.

Background: Thyroid eye disease (TED) is an inflammatory process involving lymphocyte-mediated immune response and orbital tissue damage. The anti-insulin-like growth factor-1 receptor (IGF-1R) antibodies produced by B lymphocytes are involved in the activation of orbital fibroblasts and the inflammatory process of orbital tissue damage in TED. The purpose of this study was to explore the role of IGF-1R in the mechanistic connection between orbital fibroblasts and B lymphocytes in TED.

Methods: Orbital fibroblasts sampled from orbital connective tissues and peripheral B lymphocytes isolated from peripheral blood, which were obtained from 15 patients with TED and 15 control patients, were co-cultured at a ratio of 1:20. The level of IGF-1R expression in orbital fibroblasts was evaluated by flow cytometry and confocal microscopy. Transient B lymphocyte depletion was induced with anti-CD20 monoclonal antibody rituximab, while the IGF-1R pathway was blocked by the IGF-1R binding protein. The expression levels of interleukin-6 (IL-6) and regulated upon activation, normal T cell expressed and secreted (RANTES) in the co-culture model were quantified via ELISA.

Results: IGF-1R expression was significantly elevated in TED orbital fibroblasts compared to that of controls. A 24-h co-culture of orbital fibroblasts with peripheral B lymphocytes induced elevated expression levels of IL-6 and RANTES in each group (TED patients and controls), with the highest levels occurring in TED patients (T + T group). Rituximab and IGF-1R binding protein significantly inhibited increased levels of IL-6 and RANTES in the co-culture model of TED patients.

Conclusions: IGF-1R may mediate interaction between orbital fibroblasts and peripheral B lymphocytes; thus, blocking IGF-1R may reduce the local inflammatory response in TED. Rituximab-mediated B lymphocyte depletion played a role in inhibiting inflammatory responses in this in vitro co-culture model, providing a theoretical basis for the clinical application of anti-CD20 monoclonal antibodies in TED.

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来源期刊
BMC Immunology
BMC Immunology 医学-免疫学
CiteScore
5.50
自引率
0.00%
发文量
54
审稿时长
1 months
期刊介绍: BMC Immunology is an open access journal publishing original peer-reviewed research articles in molecular, cellular, tissue-level, organismal, functional, and developmental aspects of the immune system as well as clinical studies and animal models of human diseases.
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