创伤后应激障碍 (PTSD) 是一种使人衰弱的精神疾病，在经历创伤事件后会对公共健康产生重大影响。最近的研究强调了创伤后应激障碍（PTSD）中免疫失调的参与，其特点是炎症标志物升高。然而，这种免疫失衡背后的确切机制仍不清楚。先前的研究表明，友人白血病病毒整合 1 (FLI1)（一种红细胞转化特异性 (ETS) 转录因子）与脓毒症和阿尔茨海默病的炎症反应有关。外周血单核细胞 (PBMC) 中 FLI1 水平升高与狼疮严重程度有关。然而，FLI1 在 PTSD 相关炎症中的作用仍未被探索。在我们的研究中，从有或没有 PTSD 的退伍军人身上收集了 PBMC。我们发现患有 PTSD 的退伍军人的 PBMC 中 FLI1 表达显着增加，尤其是 CD4 T 细胞中，而 CD8 T 细胞中没有显着变化。与对照组相比，LPS 刺激导致 PTSD PBMC 中 FLI1 表达升高，炎症细胞因子 IL-6 和 IFNγ 水平升高。在 PTSD PBMC 中使用 Gapmers 敲低 FLI1 导致炎症细胞因子水平显着降低，使其恢复到对照组水平。此外，将来自对照和 PTSD 退伍军人的 PBMC 与人脑小胶质细胞系 HMC3 共培养，发现 HMC3 中炎症介质水平增加。值得注意的是，与经 Gapmer 处理的对照 PTSD PBMC 相比，与经 FLI1 Gapmers 处理的 PTSD PBMC 共培养的 HMC3 细胞表现出显着较低的炎症介质水平。这些发现表明，抑制 FLI1 可能会重新平衡 PBMC 中的免疫活性，并减轻大脑中小胶质细胞的激活。这些见解可以为 PTSD 提供新颖的治疗策略。版权所有 © 2024 Li、Liu、Liu、Lu、Halushka、Sidles、LaRue、Wang 和 Fan。

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition with significant public health implications that arise following exposure to traumatic events. Recent studies highlight the involvement of immune dysregulation in PTSD, characterized by elevated inflammatory markers. However, the precise mechanisms underlying this immune imbalance remain unclear. Previous research has implicated friend leukemia virus integration 1 (FLI1), an erythroblast transformation-specific (ETS) transcription factor, in inflammatory responses in sepsis and Alzheimer's disease. Elevated FLI1 levels in peripheral blood mononuclear cells (PBMCs) have been linked to lupus severity. Yet, FLI1's role in PTSD-related inflammation remains unexplored. In our study, PBMCs were collected from Veterans with and without PTSD. We found significantly increased FLI1 expression in PBMCs from PTSD-afflicted Veterans, particularly in CD4+ T cells, with no notable changes in CD8+ T cells. Stimulation with LPS led to heightened FLI1 expression and elevated levels of inflammatory cytokines IL-6 and IFNγ in PTSD PBMCs compared to controls. Knockdown of FLI1 using Gapmers in PTSD PBMCs resulted in a marked reduction in inflammatory cytokine levels, restoring them to control group levels. Additionally, co-culturing PBMCs from both control and PTSD Veterans with the human brain microglia cell line HMC3 revealed increased inflammatory mediator levels in HMC3. Remarkably, HMC3 cells co-cultured with PTSD PBMCs treated with FLI1 Gapmers exhibited significantly lower inflammatory mediator levels compared to control Gapmer-treated PTSD PBMCs. These findings suggest that suppressing FLI1 may rebalance immune activity in PBMCs and mitigate microglial activation in the brain. Such insights could provide novel therapeutic strategies for PTSD.Copyright © 2024 Li, Liu, Liu, Lu, Halushka, Sidles, LaRue, Wang and Fan.