Researchers at Weill Cornell Medicine have made an innovative discovery by finding that cytokines, which are proteins that regulate immune response, circulating in maternal blood during pregnancy play a significant role in fetal brain development and offspring behavior. Contrary to previous beliefs, these cytokines were found to reduce the risk of psychiatric conditions in offspring potentially. It was previously believed that elevated levels of cytokines in maternal circulation increase the offspring’s risk for neuropsychiatric diseases. However, this study reveals that the low homeostatic levels of circulating maternal cytokines during normal pregnancies can help mitigate the risk of psychiatric conditions in offspring.
The study findings were published in the Journal of Brain, Behavior, and Immunity, highlighting the pivotal role of cytokine XCL1 (also known as lymphotactin), which is produced by maternal immune cells and acts as a pregnancy hormone. The researchers found that circulating XCL1 normally remained at the same low pre-pregnancy level throughout gestation, except for a brief rise and fall in the middle period. This temporary increase is essential for the proper development of the placenta and the emotional behavior of the offspring.
Chen et al. shed light on how blocking or neutralizing this spike in XCL1 leads to increased tissue damage in the fetal placenta and subsequent elevated innate anxiety and stress reactions in male mouse offspring. Moreover, abnormalities were observed in the developing brains of these offspring, particularly in the ventral hippocampus, a region associated with anxiety and anxious behavior. Although these immune and neuronal abnormalities normalize by adulthood, the study suggests a correlation between the absence of elevated XCL1 during early development and adult anxious behavior. The researchers plan to further investigate other chemokines regulating placenta development and their impact on offspring’s emotional behavior.
The study findings underscore the intricate interplay between maternal immune factors and fetal brain development, emphasizing the importance of considering prenatal immune modulation for promoting healthy neurodevelopment and reducing the risk of psychiatric disorders later in life.
Reference
Chen RJ, Nabila A, Gal Toth J, Stuhlmann H, Toth M. The chemokine XCL1 functions as a pregnancy hormone to program offspring innate anxiety. Brain, Behavior, and Immunity. 2024 May 1;118:178–89.