Laboratory for Molecular Psychosomatics, Department of Psychosomatic Medicine and Psychotherapy, Ulm University, Ulm, Germany.
Front Immunol. 2021 Oct 5;12:753822. doi: 10.3389/fimmu.2021.753822. eCollection 2021.
Chronic psychosocial stress is a risk factor for the development of numerous disorders, of which most are associated with chronic low-grade inflammation. Given the immunosuppressive effects of glucocorticoids (GC), one underlying mechanism might be the development of stress-induced GC resistance in certain immune cell subpopulations. In line with this hypothesis, male mice exposed to the chronic subordinate colony housing (CSC, 19 days) model develop GC resistance of lipopolysaccharide (LPS)-stimulated splenocytes, splenomegaly and an increased percentage of splenic CD11b cells. Here male C57BL/6N mice were euthanized at different days during CSC, and following 30 days of single housing after stressor termination to assess when CSC-induced splenic GC resistance starts to develop and whether this is a transient effect. Moreover, splenic CD11b, GC receptor (GR) and/or macrophage migration inhibiting factor (MIF) protein levels were quantified at respective days. While mild forms of CSC-induced GC resistance, increased splenic CD11b expression and/or splenomegaly were detectable on days 8 and 9 of CSC, more severe forms took until days 15 and 16 to develop, but normalized almost completely within 30 days following stressor termination (day 51). In contrast, splenic GR expression was decreased in CSC versus single-housed control (SHC) mice at all days assessed. While MIF expression was increased on days 15 and 16 of CSC, it was decreased in CSC versus SHC mice on day 20 despite persisting splenomegaly, increased CD11b expression and functional GC resistance. In summary, our data indicate that GC resistance and CD11b cell-mediated splenomegaly develop gradually and in parallel over time during CSC exposure and are transient in nature. Moreover, while we can exclude that CSC-induced reduction in splenic GR expression is sufficient to induce functional GC resistance, the role of MIF in CD11b cell-mediated splenomegaly and GC resistance requires further investigation.
慢性心理社会应激是许多疾病发生的危险因素，其中大多数与慢性低度炎症有关。鉴于糖皮质激素 (GC) 的免疫抑制作用，一个潜在的机制可能是某些免疫细胞亚群中应激诱导的 GC 抵抗的发展。根据这一假设，暴露于慢性下属群体饲养 (CSC，19 天) 模型的雄性小鼠发展出 LPS 刺激的脾细胞、脾肿大和脾 CD11b 细胞比例增加的 GC 抵抗。在这里，雄性 C57BL/6N 小鼠在 CSC 期间的不同天数被安乐死，并且在应激源终止后进行 30 天的单独饲养，以评估 CSC 诱导的脾 GC 抵抗何时开始发展，以及这是否是一种暂时的影响。此外，在各自的日子里量化了脾 CD11b、GC 受体 (GR) 和/或巨噬细胞迁移抑制因子 (MIF) 蛋白水平。虽然在 CSC 诱导的 GC 抵抗的轻度形式中，在 CSC 的第 8 天和第 9 天可以检测到脾 CD11b 表达增加和/或脾肿大，但更严重的形式直到第 15 天和第 16 天才发展，但在应激源终止后几乎完全恢复正常（第 51 天）。相比之下，在所有评估的日子里，CSC 中的脾 GR 表达均低于单独饲养对照 (SHC) 小鼠。虽然在 CSC 的第 15 天和第 16 天 MIF 表达增加，但在 CSC 中的表达低于 SHC 小鼠，尽管持续存在脾肿大、CD11b 表达增加和功能性 GC 抵抗。总之，我们的数据表明，在 CSC 暴露期间，GC 抵抗和 CD11b 细胞介导的脾肿大逐渐平行发展，且具有短暂性。此外，虽然我们可以排除 CSC 诱导的脾 GR 表达减少足以诱导功能性 GC 抵抗，但 MIF 在 CD11b 细胞介导的脾肿大和 GC 抵抗中的作用需要进一步研究。
