Splenic denervation attenuates repeated social defeat stress-induced T-lymphocyte inflammation.
Splenic denervation attenuates repeated social defeat stress-induced T-lymphocyte inflammation.
复制标题
去脾神经可减轻反复的社会挫败应激引起的T淋巴细胞炎症。
DOI：
10.1016/j.bpsgos.2021.05.004
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Case AJ
中科院分区：
文献类型：
--
作者：
Elkhatib SK;Moshfegh CM;Watson GF;Schwab AD;Katsurada K;Patel KP;Case AJ
创伤后应激障碍（PTSD）是一种毁灭性的心理障碍。PTSD患者典型地表现出炎症性疾病的风险增加以及交感神经紧张和去甲肾上腺素流出增加。然而，这些生理变化的确切病因和因果性质仍不清楚。以前，我们证明了外源性去甲肾上腺素改变T淋巴细胞中的线粒体超氧化物产生促炎性T辅助细胞17表型，并在PTSD的临床前模型中观察到类似的T辅助细胞17极化。因此，我们假设交感神经驱动的神经免疫相互作用可以介导心理创伤诱导的T淋巴细胞炎症。反复社交失败压力（RSDS）是一种临床前小鼠模型，其概括了PTSD的行为、自主神经和炎症方面。进行靶向脾去神经支配以推断脾交感神经对RSDS诱导的炎症的贡献。在85只C57 BL/6 J小鼠中进行去神经或假手术，随后进行RSDS或对照范例。评估动物的行为、自主神经、炎症和氧化还原特征。去神经并没有改变RSDS诱导的反社会或焦虑样行为。在循环中，与完整动物相比，去神经/RSDS动物的T淋巴细胞特异性细胞因子（白细胞介素2 [IL-2]、IL-17 A和IL-22）水平降低，而其他非特异性炎症细胞因子（例如，IL-6、肿瘤坏死因子α和IL-10）不受去神经支配的影响。重要的是，去神经支配特异性地改善了RSDS诱导的T淋巴细胞线粒体超氧化物、T辅助细胞17极化和促炎基因表达的增加，对非T淋巴细胞免疫群体的影响最小。总体而言，我们的数据表明交感神经调节RSDS诱导的脾脏T淋巴细胞炎症，但在这种心理创伤范式诱导的行为和非T淋巴细胞炎症表型中发挥的作用较小。
Posttraumatic stress disorder (PTSD) is a devastating psychological disorder. Patients with PTSD canonically demonstrate an increased risk for inflammatory diseases as well as increased sympathetic tone and norepinephrine outflow. Yet, the exact etiology and causal nature of these physiologic changes remain unclear. Previously, we demonstrated that exogenous norepinephrine alters mitochondrial superoxide in T lymphocytes to produce a proinflammatory T helper 17 phenotype and observed similar T helper 17 polarization in a preclinical model of PTSD. Therefore, we hypothesized sympathetic-driven neuroimmune interactions could mediate psychological trauma–induced T lymphocyte inflammation. Repeated social defeat stress (RSDS) is a preclinical murine model that recapitulates the behavioral, autonomic, and inflammatory aspects of PTSD. Targeted splenic denervation was performed to deduce the contribution of splenic sympathetic nerves to RSDS-induced inflammation. Denervation or sham operation was performed in 85 C57BL/6J mice, followed by RSDS or control paradigms. Animals were assessed for behavioral, autonomic, inflammatory, and redox profiles. Denervation did not alter the antisocial or anxiety-like behavior induced by RSDS. In circulation, denervation/RSDS animals exhibited diminished levels of T lymphocyte–specific cytokines (interleukin 2 [IL-2], IL-17A, and IL-22) compared with intact animals, whereas other nonspecific inflammatory cytokines (e.g., IL-6, tumor necrosis factor α, and IL-10) were unaffected by denervation. Importantly, denervation specifically ameliorated the increases in RSDS-induced T lymphocyte mitochondrial superoxide, T helper 17 polarization, and proinflammatory gene expression with minimal impact to non–T lymphocyte immune populations. Overall, our data suggest that sympathetic nerves regulate RSDS-induced splenic T lymphocyte inflammation but play less of a role in the behavioral and non–T lymphocyte inflammatory phenotypes induced by this psychological trauma paradigm.
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通过α（1） - 肾上腺素受体激活调节免疫细胞功能。
影响因子：
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作者：
Grisanti, Laurel A.;Perez, Dianne M.;Porter, James E.
通讯作者：
Porter, James E.
影响因子：
2.7
作者：
Bratton, B. O.;Martelli, D.;McAllen, R. M.
通讯作者：
McAllen, R. M.
影响因子：
15.1
作者：
BELLINGER, DL;LORTON, D;FELTEN, DL
通讯作者：
FELTEN, DL
影响因子：
2
作者：
Zambrano-Zaragoza JF;Romo-Martínez EJ;Durán-Avelar Mde J;García-Magallanes N;Vibanco-Pérez N
通讯作者：
Vibanco-Pérez N
DOI：
10.1161/hypertensionaha.111.00474
发表时间：
2013-04
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Foss JD;Fink GD;Osborn JW
通讯作者：
Osborn JW