Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA.
Cell and Developmental Biology, Weill Cornell Medicine, New York, NY 10065, USA.
Brain Behav Immun. 2024 May;118:178-189. doi: 10.1016/j.bbi.2024.02.032. Epub 2024 Feb 29.
Elevated levels of cytokines in maternal circulation increase the offspring's risk for neuropsychiatric disease. Because of their low homeostatic levels, circulating maternal cytokines during normal pregnancies have not been considered to play a role in fetal brain development and offspring behavior. Here we report that the T/NK cell chemotactic cytokine XCL1, a local paracrine immune signal, can function as a pregnancy hormone and is required for the proper development of placenta and male offspring approach-avoidance behavior. We found that circulating XCL1 levels were at a low pregestational level throughout pregnancy except for a midgestational rise and fall. Blunted elevation in maternal plasma XCL1 in dams with a genetic 5HT1A receptor deficit or following neutralization by anti-XCL1 antibodies increased the expression of tissue damage associated factors in WT fetal placenta and led to increased innate anxiety and stress reactivity in the WT male offspring. Therefore, chemokines like XCL1 may act as pregnancy hormones to regulate placenta development and offspring emotional behavior.
母体循环中细胞因子水平升高会增加后代患神经精神疾病的风险。由于细胞因子在正常妊娠期间的内稳态水平较低，因此人们一直认为它们不会在胎儿大脑发育和后代行为中发挥作用。在这里，我们报告 T/NK 细胞趋化因子 XCL1，一种局部旁分泌免疫信号，可以作为妊娠激素，并且是胎盘和雄性后代趋近回避行为正常发育所必需的。我们发现，除了中期上升和下降之外，母体循环中的 XCL1 水平在整个妊娠期间都处于低妊娠前水平。在 5HT1A 受体缺陷的母鼠中或通过抗 XCL1 抗体中和后，母体血浆 XCL1 的升高减弱，会增加 WT 胎儿胎盘组织损伤相关因子的表达，并导致 WT 雄性后代的先天焦虑和应激反应性增加。因此，像 XCL1 这样的趋化因子可能作为妊娠激素发挥作用，调节胎盘发育和后代的情绪行为。
