Laboratory of Molecular Medicine and Biotechnology, IRCCS S. Maria Nascente, Don C. Gnocchi ONLUS Foundation, Via Capecelatro 66, Milano 20148, Italy.
Brain Behav Immun. 2011 Mar;25(3):539-47. doi: 10.1016/j.bbi.2010.12.004. Epub 2010 Dec 16.
Inflammatory mediators are responsible for the neuroinflammation observed in Alzheimer's disease (AD), a phenomenon that might be the culprit of disease or, possibly, a reaction to pathology. To better investigate inflammation in AD we performed an extensive immunophenotypic and functional analysis of amyloid-beta (Aβ) stimulated T lymphocytes in patients with a diagnosis of AD comparing data to those obtained in individuals with mild cognitive impairment (MCI) or aged-matched healthy individuals (HC). Results showed that IL-21- and IL-9-producing Aβ stimulated CD4(+) T cells, as well as IL-23- and IL-6-producing monocytes and CD4(+) T cells expressing the RORγ and NFATc1 transcriptional factors (TF), were significantly increased, whereas IL-10-producing monocytes were decreased in AD. Notably, GATA-3 TF-expressing CD4(+) T lymphocytes were significantly increased in MCI alone. Analysis of the post-thymic differentiation pathway indicated that Aβ specific naïve and central memory CD4(+) T lymphocytes were diminished whereas effector memory and terminally differentiated CD4(+) T lymphocytes were increased in AD and MCI compared to HC. Data herein indicate that cytokines (IL-21, IL-6, IL-23) and TF (RORγ) involved in the differentiation of Th-17 cells), as well as cytokines (IL-21, IL-22) generated by such cells, and IL-9, produced by Th-9 cells, are significantly increased in AD. This is accompanied by a shift of post-thymic differentiation pathways favoring the accumulation of differentiated, effector T lymphocytes. These data shed light on the nature of AD-associated neuroinflammation. A better understanding of the complexity of this phenomenon could facilitate the search for novel therapeutic strategies.
炎症介质是阿尔茨海默病（AD）中观察到的神经炎症的原因，这种现象可能是疾病的罪魁祸首，也可能是对病理学的反应。为了更好地研究 AD 中的炎症，我们对 AD 患者、轻度认知障碍（MCI）患者和年龄匹配的健康对照（HC）的 Aβ 刺激 T 淋巴细胞进行了广泛的免疫表型和功能分析。结果表明，IL-21 和 IL-9 产生的 Aβ 刺激 CD4+T 细胞，以及 IL-23 和 IL-6 产生的单核细胞和表达 RORγ和 NFATc1 转录因子（TF）的 CD4+T 细胞明显增加，而 AD 中 IL-10 产生的单核细胞减少。值得注意的是，仅在 MCI 中 GATA-3 TF 表达的 CD4+T 淋巴细胞明显增加。后胸腺分化途径分析表明，与 HC 相比，AD 和 MCI 中 Aβ 特异性幼稚和中央记忆 CD4+T 淋巴细胞减少，而效应记忆和终末分化 CD4+T 淋巴细胞增加。本文数据表明，参与 Th17 细胞分化的细胞因子（IL-21、IL-6、IL-23）和 TF（RORγ），以及此类细胞产生的细胞因子（IL-21、IL-22）和 Th9 细胞产生的 IL-9 在 AD 中明显增加。这伴随着后胸腺分化途径的转变，有利于分化的效应 T 淋巴细胞的积累。这些数据揭示了 AD 相关神经炎症的性质。更好地理解这一现象的复杂性可能有助于寻找新的治疗策略。
