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Skull
Meninges structure CCL21
+
-
+
CD4 ，CD45RA ，CD27 ，CD69 +
IL⁃1
CCR7
Cerebrum
sCLN
IL⁃6 Dura mater
TNF⁃α
Arachnoid
mater
SLYM
IL⁃4
IL⁃13
dCLN CD206
Pia mater
RDNF
ICF⁃1
TGF⁃β
Brai
parcnchyma
+
MLV CD4 T cell DC Macrophage Astrocyte
PROX1 +
+
VEGFR3 + Vein CD8 T cell ILC MC Microglia
LYVE1 +
CCL21 +
MLV Artery NK cell B cell Monocyte Neuron cell
The dura mater can be divided into outer and inner layers，the arachnoid mater consists of a layer of closely connected outer cells，surrounding the
subarachnoid space filled with cerebrospinal fluid（CSF）. Recently，a structure called subarachoid lymphatic⁃like membrane（SLYM）was discovered
between the arachnoid and pia mater，dividing the subarachnoid space into superficial and deep compartments. The innermost layer of the meninges is
the pia mater，beneath which lies a membrane formed by closely connected astrocytes and their processes，known as the glia limitans. Together，the pia
mater and glia limitans constitute the final barrier above the brain parenchyma. The dura mater contains numerous immune cells，including dendritic
cells（DC），mast cells（MC），innate lymphoid cells（ILC），meningeal macrophages，T cells and B cells. Immune cells on the pia mater are fewer
compared to the dura mater，mainly consisting of macrophages，DC and MC. The CSF primarily contains memory T cells，a small number of B cells，and
+
+
⁃
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mononuclear cells. T cells in the CSF include CD4 /CD45RA /CD27 /CD69 memory T cells expressing high levels of CCR7 and L⁃selectin，responsible
+
for immune surveillance. If no antigens are detected，they flow back into the deep cervical lymph nodes（dCLN）through meningeal lymphatics. CD4 αβ
T cells in the CSF release IL⁃4，IL⁃13 and IL⁃17，exerting brain⁃protective effects and participating in social behavior by producing IFN⁃γ. Meningeal
lymphatics，tube⁃like structures arranged along veins on the dura mater，are particularly developed around the skull base. They express classic markers
under physiological conditions，including PROX1，VEGFR3，LYVE1，podoplanin and CCL21，lacking smooth muscle cells and valves. Comparatively
smaller than lymphatics associated with the diaphragm，meningeal lymphatics form a relatively simple network covering fewer tissues. Carrying numerous
immune cells，they connect cytokines related to brain parenchyma with the peripheral immune system，draining immune cells and cytokines from the
subarachnoid space into dCLN and partially into sCLN.
图1 脑膜结构和免疫功能相关示意图
Figure 1 Structure and immune function of meninges

泛，大脑灰质的轴突丢失也随之发生，脑膜炎症的 型是 EAE 模型鼠，目前主要通过自身反应性 T 细胞
严重性与 MS 病情严重程度和死亡率呈正相关。 过继转移诱导被动性EAE模型鼠，或通过髓磷脂抗
Lucchinetti 等 ［34］ 通过活体脑组织成像技术，发现脑 原免疫注射诱导主动性 EAE 模型鼠 。有研究在
［5］
膜炎症常常发生在 MS 早期，甚至可能早于白质病 EAE 鼠的病理过程中观察到，有活性的 T 细胞进入
变的出现。在MS病程中，大脑活性T细胞入侵中枢 脑实质，而无活性的T细胞则进入CSF，经过软脑膜
神经系统，诱导自我损伤性炎症反应发生，T细胞浸 的筛选，T 细胞得以接触抗原，引起脑组织损伤，诱
润最早在脑膜中被观察到，早于脑实质浸润以及临 导 MS 的病理过程 ［36］ 。Furtado 等 ［37］ 发现，在 EAE 病
［35］
床症状的出现，而在CSF中也发现了T细胞浸润 。 理进程中，T细胞活化最早发生在颈淋巴结，手术切
由此可见，脑膜炎症与MS的发病和进展紧密相关。 除颈淋巴结可以改善EAE的病理情况，进一步证实
由于 MS 患者标本不易获取，最理想的研究模 了EAE的发生与脑膜T细胞活化相关。Louveau 等 ［18］