A causal relationship between immune dysregulation and schizophrenia has been supported by genome-wide association studies and epidemiological evidence. It remains unclear to what extent the brain immune environment is implicated in this hypothesis. We investigated the immunophenotype of microglia and the presence of perivascular macrophages and T lymphocytes in post-mortem brain tissue. Dorsal prefrontal cortex of 40 controls (22F:18M) and 37 (10F:27M) schizophrenia cases, of whom 16 had active psychotic symptoms at the time of death, was immunostained for seven markers of microglia (CD16, CD32a, CD32b, CD64, CD68, HLA-DR, Iba1 and P2RY12), two markers perivascular macrophages (CD163 and CD206) and T-lymphocytes (CD3). Automated quantification was blinded to the case designation and performed separately on the grey and white matter. 3D reconstruction of Iba1-positive microglia was performed in selected cases. An increased cortical expression of microglial Fcγ receptors (CD64 F=7.92 p=0.007; CD64/HLA-DR ratio F=5.02, p=0.029) highlights the importance of communication between the central and peripheral immune systems in schizophrenia. Patients in whom psychotic symptoms were present at death demonstrated an age-dependent increase of Iba1 and increased CD64/HLA-DR ratios relative to patients without psychotic symptoms. Microglia in schizophrenia demonstrated a primed/reactive morphology. A potential role for T-lymphocytes was observed, but we did not confirm the presence of recruited macrophages in the brains of schizophrenia patients. Taking in account the limitations of a post-mortem study, our findings support the hypothesis of an alteration of the brain immune environment in schizophrenia, with symptomatic state- and age-dependent effects.

全基因组关联研究和流行病学证据支持免疫失调与精神分裂症之间的因果关系。目前尚不清楚大脑免疫环境在多大程度上与这一假设有关。我们研究了死后脑组织中小胶质细胞的免疫表型以及血管周围巨噬细胞和 T 淋巴细胞的存在。对 40 名对照组 (22F:18M) 和 37 名 (10F:27M) 精神分裂症病例（其中 16 名在死亡时有活动性精神病症状）的背侧前额皮质进行了七种小胶质细胞标记物（CD16、CD32a、CD32b、CD64、 CD68、HLA-DR、Iba1 和 P2RY12）、两种标记血管周围巨噬细胞（CD163 和 CD206）和 T 淋巴细胞 (CD3)。自动定量对病例名称不知情，并分别对灰质和白质进行。在选定的病例中进行了 Iba1 阳性小胶质细胞的 3D 重建。小胶质细胞 Fcγ 受体的皮质表达增加（CD64 F =7.92 p =0.007；CD64/HLA-DR 比率F =5.02， p =0.029）凸显了精神分裂症中中枢和外周免疫系统之间沟通的重要性。与没有精神病症状的患者相比，死亡时出现精神病症状的患者表现出 Iba1 的年龄依赖性增加和 CD64/HLA-DR 比值的增加。精神分裂症中的小胶质细胞表现出启动/反应形态。观察到 T 淋巴细胞的潜在作用，但我们没有证实精神分裂症患者大脑中是否存在招募的巨噬细胞。 考虑到尸检研究的局限性，我们的研究结果支持了精神分裂症大脑免疫环境改变的假设，并具有症状状态和年龄依赖性影响。