B 细胞在 GF-IL23 模型中白细胞介素-23 依赖性神经炎症中的核心作用。
Central role of B cells in interleukin-23 dependent neuroinflammation in the GF-IL23 model.
机构信息
Department of Neurology, University Hospital Bonn, Bonn, Germany.
Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
出版信息
Neuroreport. 2022 Sep 7;33(13):577-582. doi: 10.1097/WNR.0000000000001818. Epub 2022 Jul 18.
Interleukin (IL)-23 is one of the critical cytokines in autoimmune neuroinflammation. To further clarify the local function of IL-23 on the course of neuroinflammation, we recently established a transgenic mouse model with astrocyte-specific expression of IL-23 (GF-IL23). The GF-IL23 mice spontaneously developed a progressive ataxic phenotype with cerebellar infiltration with high amounts of B cells most prominent in the subarachnoid and perivascular space. To enlighten the B cell role in GF-IL23 mice, we generated GF-IL23 mice on a B cell knockout (k.o.) background (GF-IL23 B cell k.o.). GF-IL23 B cell k.o. mice compared with GF-IL23 mice had no infiltrates or only minor infiltration, and no antibody deposition was detected in the cerebellum. Furthermore, microglia, astrocyte activation, hypervascularization and demyelination were reduced in GF-IL23 B cell k.o. mice compared with GF-IL23 mice. Cytokines and chemokine receptors like IL-12a, cerebrospinal fluid 2 and CXCR3 were downregulated. Our study indicates that B cells are essential in IL-23-dependent neuroinflammation in the GF-IL23 model.
白细胞介素 (IL)-23 是自身免疫性神经炎症的关键细胞因子之一。为了进一步阐明 IL-23 在神经炎症过程中的局部功能，我们最近建立了一种星形胶质细胞特异性表达 IL-23（GF-IL23）的转基因小鼠模型。GF-IL23 小鼠自发出现进行性共济失调表型，小脑浸润，B 细胞数量高，尤其是蛛网膜下腔和血管周围空间。为了阐明 B 细胞在 GF-IL23 小鼠中的作用，我们在 B 细胞敲除 (k.o.) 背景下（GF-IL23 B 细胞 k.o.）生成了 GF-IL23 小鼠。与 GF-IL23 小鼠相比，GF-IL23 B 细胞 k.o. 小鼠没有浸润或仅有少量浸润，小脑内未检测到抗体沉积。此外，与 GF-IL23 小鼠相比，GF-IL23 B 细胞 k.o. 小鼠的小胶质细胞、星形胶质细胞活化、血管增生和脱髓鞘减少。IL-12a、脑脊液 2 和 CXCR3 等细胞因子和趋化因子受体下调。我们的研究表明，B 细胞在 GF-IL23 模型中的 IL-23 依赖性神经炎症中是必不可少的。
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