Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, Guangzhou 510080, China; National Key Clinical Department and Key Discipline of Neurology, Guangzhou 510080, China.
Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, Guangzhou 510080, China; National Key Clinical Department and Key Discipline of Neurology, Guangzhou 510080, China.
J Neuroimmunol. 2024 Oct 15;395:578441. doi: 10.1016/j.jneuroim.2024.578441. Epub 2024 Aug 20.
Dendritic cells (DCs) are crucial to form ectopic germinal centers (GCs) in the hyperplastic thymus (HT), which are typically found in anti-acetylcholine receptor autoantibody-positive myasthenia gravis (MG) patients. However, the characteristics of such DCs in the HT and their roles in thymic hyperplasia formation remain unclear.
We collected thymic tissue from MG patients and patients who underwent cardiac surgery. The tissues were cut into sections for immunohistochemistry and immunofluorescence or digested into a single cell suspension for flow cytometry.
In addition to formation of ectopic GCs, we found that the proportion of the medulla in the thymic parenchyma was higher than that in the cortex (area/area, 1.279 vs. 0.6576) in the HT of MG patients. The density of conventional dendritic cells (cDCs) in the HT was 131 ± 64.36 per mm, whereas in normal thymic tissue, the density was 59.17 ± 22.54 per mm. The more abundant cDCs expressed co-stimulatory molecules (CD80 and CD86) strongly. Moreover, the more abundant subset was mainly CD141+ DCs (cDC1s), accounting for an increase from 15% to 29%. However, these increased cDC1s appeared to be unrelated to Hassall's corpuscles and ectopic GCs.
Thymic hyperplasia in MG patients is manifested as an increase in the proportion of the thymic medulla accompanied by increases in the density and functional activation as well as changes in the subset composition of cDCs.
树突状细胞(DCs)对于在增生的胸腺(HT)中形成异位生发中心(GCs)至关重要,这些 GC 通常存在于抗乙酰胆碱受体自身抗体阳性的重症肌无力(MG)患者中。然而,HT 中的这些 DC 的特征及其在胸腺增生形成中的作用尚不清楚。
我们收集了 MG 患者和接受心脏手术的患者的胸腺组织。将组织切成切片进行免疫组织化学和免疫荧光检查,或消化成单细胞悬液进行流式细胞术分析。
除了形成异位 GCs 外,我们还发现 MG 患者 HT 中的胸腺实质髓质比例高于皮质(面积/面积,1.279 比 0.6576)。HT 中的常规树突状细胞(cDCs)密度为 131±64.36 个/mm,而在正常胸腺组织中,密度为 59.17±22.54 个/mm。更多的 cDCs 强烈表达共刺激分子(CD80 和 CD86)。此外,更多的 cDC 主要是 CD141+ DCs(cDC1s),占比从 15%增加到 29%。然而,这些增加的 cDC1s 似乎与 Hassall 小体和异位 GCs 无关。
MG 患者的胸腺增生表现为胸腺髓质比例增加,同时 cDCs 的密度和功能激活增加,以及亚群组成发生变化。