Psychoneuroimmunological studies have clearly demonstrated that both cellular and humoral immunity are related to major depression. Soluble ST2 is regarded as a key molecule regulating immune system as well as cell proliferation. Indeed, soluble ST2 is reported to reduce IL-33-induced IL-6 and TNF-α production in macrophages and IL-33-induced IL-5 and IL-13 production in type 2 innate lymphoid cells. Elevated serum concentrations of soluble ST2 have been reported in patients with neuropsychiatric disorders, suggesting pathophysiological roles of soluble ST2 in behavioral phenotypes. Nevertheless, the relation between soluble ST2 and depressive behavior remain to be uncovered. To complement this point, we performed broad behavioral phenotyping, utilizing transgenic mice with a high concentration of serum ST2 in the present study. Soluble ST2 overexpression mice (ST2 Tg mice) were generated on a C3H/HeJ background. ST2 Tg mice crossed onto the BALB/c genetic background were used. Before starting tests, each mouse was observed in a clean cage for a general health check and neurological screening tests. In Experiment I, comprehensive behavioral phenotyping was performed to reveal the role of soluble ST2 on sensorimotor functions, anxiety-like behaviors, depression-like behaviors, social behaviors, and learning and memory functions. In Experiment II, to confirm the role of soluble ST2 on depression-like behaviors, a depression test battery (two bottle choice test, forced swimming test, and tail suspension test) was applied. The general health check indicated good general health and normal gross appearance for ST2 Tg mice. Further, the neurological reflexes of all the mice were normal. We found that soluble ST2 overexpression resulted in decreased social interaction. Moreover, depression-like behaviors of ST2 Tg mice were observed in two well-established behavioral paradigms, the forced swimming test and the tail suspension test. Nevertheless, hedonic reaction to sucrose was observed in ST2 Tg mice similar to WT mice. These results suggest the depression in the ST2 Tg mice. In conclusion, through a series of experiments, we established the animal model for assessing role of soluble ST2 in neuropsychiatric disorders, and revealed the possible involvement of soluble ST2 in depressive behavior.

中文翻译：

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过表达可溶性ST2的小鼠的行为改变。

心理神经免疫学研究清楚地表明，细胞免疫和体液免疫均与严重抑郁有关。可溶性ST2被认为是调节免疫系统以及细胞增殖的关键分子。实际上，据报道可溶性ST2减少巨噬细胞中IL-33诱导的IL-6和TNF-α的产生以及2型先天性淋巴细胞中IL-33诱导的IL-5和IL-13的产生。在神经精神疾病患者中已经报道了可溶性ST2的血清浓度升高，表明可溶性ST2在行为表型中的病理生理作用。然而，可溶性ST2与抑郁行为之间的关系仍有待发现。为了补充这一点，我们在本研究中利用具有高浓度血清ST2的转基因小鼠进行了广泛的行为表型分析。在C3H / HeJ背景下生成可溶性ST2过表达小鼠（ST2 Tg小鼠）。使用与BALB / c遗传背景杂交的ST2 Tg小鼠。在开始测试之前，在干净的笼子中观察每只小鼠，以进行一般健康检查和神经系统筛查测试。在实验I中，进行了全面的行为表型分析，以揭示可溶性ST2在感觉运动功能，焦虑样行为，抑郁样行为，社交行为以及学习和记忆功能中的作用。在实验II中，为了确认可溶性ST2对抑郁症样行为的作用，应用了抑郁症测试电池（两瓶选择测试，强制游泳测试和尾部悬浮测试）。总体健康检查表明ST2 Tg小鼠的总体健康状况良好，总体外观正常。进一步，所有小鼠的神经反射均正常。我们发现可溶性ST2过表达导致社交互动减少。此外，在两个公认的行为范例中，强迫游泳试验和尾巴悬吊试验中观察到了ST2 Tg小鼠的抑郁样行为。然而，在类似于WT小鼠的ST2 Tg小鼠中观察到对蔗糖的享乐反应。这些结果表明ST2 Tg小鼠的抑郁。总之，通过一系列实验，我们建立了评估可溶性ST2在神经精神疾病中作用的动物模型，并揭示了可溶性ST2可能与抑郁行为有关。在两个公认的行为范例中，强迫游泳试验和尾巴悬吊试验观察到了ST2 Tg小鼠的抑郁样行为。然而，在类似于WT小鼠的ST2 Tg小鼠中观察到对蔗糖的享乐反应。这些结果表明ST2 Tg小鼠的抑郁。总之，通过一系列实验，我们建立了评估可溶性ST2在神经精神疾病中的作用的动物模型，并揭示了可溶性ST2可能与抑郁行为有关。在两个公认的行为范例中，强迫游泳试验和尾巴悬吊试验观察到了ST2 Tg小鼠的抑郁样行为。然而，在类似于WT小鼠的ST2 Tg小鼠中观察到对蔗糖的享乐反应。这些结果表明ST2 Tg小鼠的抑郁。总之，通过一系列实验，我们建立了评估可溶性ST2在神经精神疾病中的作用的动物模型，并揭示了可溶性ST2可能与抑郁行为有关。