Scientists have discovered new mechanisms for regulating the nervous system's immune response

interaction between the nervous and immune systems has long been a major scientific problem, and it is particularly unclear whether there is an anatomical path of the nervous system regulating the immune response. On April 29, Nature reported on the first anatomical path path of nerve signals regulating adaptive immune responses. The study was carried out by the Bohai Task Force of the Institute of Immunology of Tsinghua University, the Hu Wei Group of the School of Life Sciences and Technology of Shanghai University of Science and Technology, and the Zhong Yi Task Force of the McGovern Institute of Brain Science of Tsinghua University.
The researchers found direct neural paths from the amygdala and myosome-promoting adrenal corticosteroid release hormone (CRH) neurons in the mouse brain to the spleen, and found that mice that removed the spleen nerves produced a sharp decrease in the number of antibody secretion cells after vaccination, suggesting that the spleen nerve impulse signal had a boost to the body's fluid response. Through pharmacological and genetic experiments, they found that the acetylcholine a9 subject expressed by B cells in the spleen was essential for this promotion of the spleen nerve. Through cell culling experiments in the body, the researchers also found that between the spleen nerves of epinephrine energy and the B cells that need to perceive acetylcholine, it is possible that the "meta-change" effect is the T cells that secrete acetylcholine by feeling the epinephrine. Using retrograde tracking of pseudo-rabies viruses, the team found a neural connection between the spleen nerve and the chamberal nucleus (PVN) and the central amygdala (CeA).
the function of these two regions is closely related to stress and fear response, and the two common types of neurons are neurons expressing CRH. CRH neurons are upstream neurons that control the pituitary-adrenal axis, and their activation can cause the adrenal glands to release a large amount of glucoticoids, adjust the body's stress, and inhibit immune system activity. This known suppression of immune endocrine function does not explain the immune enhancement seen by researchers. So they speculate that CRH neurons can directly manipulate the spleen nerve and promote the production of plasma cells by transmitting immune-enhanced signals through neural paths.
To test this hypothesis, Yuan Wei, a graduate student at the University of Science and Technology's School of Life, and Zhang Xu, a graduate student at Tsinghua University, under the guidance of Hu Wei, through photogenetic experiments, found that the CRH neurons that stimulate CeA/PVN will record a significant strengthening of electrical signals in the spleen nerve within a few seconds, proving that there is a path connect between CeA/PVN and the spleen. Furthermore, the three research groups of Bohai, Hu Wei and Zhong Yi worked together to prove that CeA/PVN CRH neuron activity correspondingly regulates the process of producing plasma cells in the response of B cells in the spleen through crH neuron rejection, DREADD chemical genetic inhibition and activation methods.
autonomous neural activity can be influenced by the external environment and behavior. So, is there any behavior that stimulates this brain-spleen neural axis and thus enhances the immune response? By monitoring the CRH neuron activity of CeA/PVN under different behavior paradigms in mice, the researchers found that the stress behavior paradigm activated crH neurons in both nucleases at the same time. What's more, in the second week after antigen vaccination, stress stimulation is experienced twice a day, and antibodies specific to antigens can be greatly increased in mice. This behavior enhances the effectiveness of antibody responses, relying on CRH neurons, spleen nerves, and Acetylcholine subjects expressed by B cells.
In this study, the researchers worked together to identify and demonstrate a brain-spleen nerve axis that enhances adaptive immunity, revealing the dual immunomodulation function of CRH neurons: first, the classically known pituitary-adrenal neuroendocrine immunosuppression, and second, the newly discovered immune enhancement effect directly on the spleen by the nerve loop. (Source: Huang Xin, China Science Journal)
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