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A&R：粒细胞集落刺激因子在系统性幼年特发性关节炎小鼠模型中性粒细胞髓外骨髓生成中的作用

2022-07-30 MedSci原创 MedSci原创

中性粒细胞粒细胞集落刺激因子全身性幼年特发性关节炎
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该研究描述粒细胞集落刺激因子(G-CSF)在全身性幼年特发性关节炎(JIA)小鼠模型中的作用，并提出G-CSF诱导的骨髓生成和中性粒细胞在调节关节炎发展中的重要作用。

目的：全身性幼年特发性关节炎(JIA)是一种儿童期发病的全身性炎症性疾病。全身性JIA 与中性粒细胞增多有关，包括未成熟的粒细胞，可能由生长因子粒细胞集落刺激因子(G-CSF)驱动。本研究旨在调查G-CSF在系统性JIA病理学中的作用。

方法：在BALB/c小鼠中注射弗氏完全佐剂(CFA)在野生型(WT)小鼠中诱导轻度炎症和中性粒细胞增多，并且在干扰素-γ-敲除(IFNγ-KO) 老鼠中引起更明显的疾病，使之更像JIA患者的疾病。通过单细胞RNA测序在CFA免疫小鼠中研究髓外骨髓生成，并评估G-CSF受体(G-CSFR)阻断对中性粒细胞发育和全身JIA病理学的影响。此外，还测量了患者的血浆G-CSF水平。

结果：在全身性JIA患者和相应的小鼠模型中，血浆G-CSF水平均增加。在小鼠模型中，研究人员证明G-CSF导致观察到的中性粒细胞增多和髓外骨髓生成以及诱导未成熟中性粒细胞和髓源性抑制样细胞。G-CSFR拮抗抗体的施用阻断了CFA免疫小鼠中中性粒细胞的成熟和分化。在IFNγ-KO小鼠中，由于中性粒细胞和破骨细胞形成减少，治疗与几乎完全抑制关节炎有关。疾病症状得到改善，但在IFNγ-KO小鼠中抑制G-CSFR后检测到白细胞介素6 (IL-6)、肿瘤坏死因子和IL-17略有增加，并且与体重减轻、尾部损伤和未成熟的红细胞的轻度增加有关。

结论：该研究描述G-CSF在全身性JIA小鼠模型中的作用，并提出G-CSF诱导的骨髓生成和中性粒细胞在调节关节炎发展中的重要作用。

原始出处：

Malengier-Devlies B, Bernaerts E, Ahmadzadeh K, et al.  Role for Granulocyte Colony-Stimulating Factor in Neutrophilic Extramedullary Myelopoiesis in a Murine Model of Systemic Juvenile Idiopathic Arthritis. Arthritis Rheumatol. 2022 Jul;74(7):1257-1270. doi: 10.1002/art.42104. Epub 2022 May 31. PMID: 35243819.

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    2023-03-29 xinxin088

    #特发性#

    0

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    2022-10-22 qingrejiedu

    #系统性#

    0

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    2022-07-31 lmm397

    #关节炎#

    0

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    2022-07-31 yykkxiaodou

    #中性粒细胞#

    0

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    2022-07-31 一叶知秋

    #小鼠模型#

    0

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