Treatment With CD52 Antibody Protects Neurons in Experimental Autoimmune Encephalomyelitis Mice During the Recovering Phase.
Treatment With CD52 Antibody Protects Neurons in Experimental Autoimmune Encephalomyelitis Mice During the Recovering Phase.
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DOI：
10.3389/fimmu.2021.792465
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发表时间：
2021
影响因子：
7.3
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Hao W;Luo Q;Menger MD;Fassbender K;Liu Y
多发性硬化症（MS）是一种由T淋巴细胞和B淋巴细胞驱动的慢性自身免疫性疾病。髓鞘再生失败和神经退行性变导致多发性硬化症患者的永久性临床残疾。一种理想的治疗方法不仅要调节免疫系统，而且要促进神经保护和髓鞘再生。为了研究CD52抗体在MS中的神经保护作用，我们在C57BL/6J和SJL实验性自身免疫性脑脊髓炎（EAE）小鼠发病高峰期用CD52抗体治疗。用CD52抗体治疗减少了血液中的T淋巴细胞而不是B淋巴细胞，减少了脊髓中T淋巴细胞和小胶质细胞/巨噬细胞的浸润。抗cd52治疗降低了恢复期EAE评分。通过减少淀粉样前体蛋白的积累，它在治疗后（4天内）立即保护神经元。它可能促进髓鞘再生，因为它增加了olig2/ cc -1阳性的成熟少突胶质细胞的数量，并在接下来的几天（如治疗后14天）防止髓鞘损失。在进一步的实验中，给条件敲除神经元中BDNF的EAE小鼠注射CD52抗体。神经元BDNF缺乏减弱了抗cd52治疗对降低EAE评分和炎症浸润的作用，但不影响抗cd52治疗诱导的脊髓髓磷脂覆盖的改善。总之，抗cd52治疗消耗cd4阳性T淋巴细胞，防止髓磷脂丢失并保护EAE小鼠的神经元。神经元BDNF调节EAE小鼠CD52抗体的神经保护和抗炎作用。
Multiple sclerosis (MS) is a chronic autoimmune disease driven by T and B lymphocytes. The remyelination failure and neurodegeneration results in permanent clinical disability in MS patients. A desirable therapy should not only modulate the immune system, but also promote neuroprotection and remyelination. To investigate the neuroprotective effect of CD52 antibody in MS, both C57BL/6J and SJL mice with experimental autoimmune encephalomyelitis (EAE) were treated with CD52 antibody at the peak of disease. Treatment with CD52 antibody depleted T but not B lymphocytes in the blood, reduced the infiltration of T lymphocytes and microglia/macrophages in the spinal cord. Anti-CD52 therapy attenuated EAE scores during the recovery phase. It protected neurons immediately after treatment (within 4 days) as shown by reducing the accumulation of amyloid precursor proteins. It potentially promoted remyelination as it increased the number of olig2/CC-1-positive mature oligodendrocytes and prevented myelin loss in the following days (e.g., 14 days post treatment). In further experiments, EAE mice with a conditional knockout of BDNF in neurons were administered with CD52 antibodies. Neuronal deficiency of BDNF attenuated the effect of anti-CD52 treatment on reducing EAE scores and inflammatory infiltration but did not affect anti-CD52 treatment-induced improvement of myelin coverage in the spinal cord. In summary, anti-CD52 therapy depletes CD4-positive T lymphocytes, prevents myelin loss and protects neurons in EAE mice. Neuronal BDNF regulates neuroprotective and anti-inflammatory effect of CD52 antibody in EAE mice.