The transformation of microcephaly caused by the Zika virus has recently made shocking headlines. The relationship between pregnancy infection and brain development is poorly understood, but the epidemic has been known for many years. More and more evidence shows that the mother's immune activation is sufficient to change brain development, which may be related to autism spectrum disorders. On this issue, Choi et al. reported in "2Science" that they discovered an important part of this immune pathway: a special type of cell in the mother’s immune system, namely T-helper 17 cells in the offspring (TH17 ). Brain development can be changed. These findings are of exciting importance for the development of new treatments to prevent autism spectrum disorders caused by maternal infections.
mechanism of action
The etiology of autism spectrum disorder is complex and is not fully understood. Changes in the mother’s immune system can play a role during pregnancy, especially during the critical period of fetal development. After the immune system is activated, the cytokine IL-6 is first activated in the serum of pregnant mice, and IL-17 acts downstream of IL-6. Since IL_17 is secreted in the mother's peripheral blood, it can cross the placenta and change the brain development of offspring. Choi et al. stimulated infected or inflamed pregnant mice, and the next generation showed behaviors reminiscent of autism spectrum disorders. Using gene mutations and antibody blockade in mice, the results showed that retinoic acid receptors (related orphan nuclear receptors (RORγtγT)) depend on effector T lymphocytes (such as TH17 cells). The presence of IL-17 in the mother is necessary for the mother’s immune activation to cause abnormal behavior in the offspring. In mothers, some of the T helper cells that produce the cytokine IL-17 cause behavioral defects in offspring related to cerebral cortex and autism spectrum disorders. During normal work, TH17 cells can protect the human body from bacterial and fungal infections, especially on mucosal surfaces such as the intestine. TH17 cells can cause autoimmunity. Although the correlation between IL-17 and the TH17 cells that produce it and autism spectrum disorders has been confirmed, the level of IL-17 in the blood of children with the disease is elevated. However, this article first discovered the role of TH17 in the mother’s immunity to the fetus. Research prospects Studies have shown that the use of interleukin IL-17 for targeted therapy during pregnancy, such as injection of IL-17 functional blocking antibodies, can reduce immune-induced autism spectrum disorders in offspring. display. This research increases the possibility of using drugs to prevent infectious autism spectrum disorders in the IL-17 pathway. However, cytokines are multifunctional, and they are essential for many unrelated processes. Therefore, inhibiting IL-17 in an infected mother may lead to self-infection. Therefore, instead of inhibiting the growth of TH17 cells, vitamin D or retinoic acid (a metabolite of vitamin A) is a possible alternative therapy.