Nature: A major breakthrough! Chinese scientists have discovered for the first time that the central nervous system directly regulates the pathways of adaptive immunity, and that body behavior can enhance the immune response.

On average, every five working days, a sentence "ah, immunization is so complicated" appears in the editorial department of odd cake.the study to be introduced today takes the complexity of immunization to a new level.in this week's nature, the research team of Qihai research group of Tsinghua University, Zhong Yi research group and Hu Ji research group of Shanghai University of science and technology jointly published a study, and found the first clear adaptive immune pathway directly mediated by central nerve signal [1], that is, the brain can directly regulate the production of antibodies! What's more, this pathway can be directly stimulated by behavior. For example, in the experiment, the antibody in the "independent platform" mice increased by 70%! It's just amazing ~ the story that tuyuan pixabay is going to tell today is in the largest immune organ of the body, which is the spleen.the spleen contains a large number of lymphocytes, and the antigens collected by antigen presenting cells from all over the body gather here. Once they are recognized by T cells, the signal of immune war will ring out. The activated T cells will further activate B cells to differentiate into plasma cells. The specific antibodies produced by plasma cells are one of the most powerful weapons against foreign invaders.in the past cognition, the immune regulation mainly depends on various hormones and cytokines. In recent years, some research results on neural direct regulation have appeared.so, is there a direct role of nerves in the immune behavior of spleen? The researchers removed the spleen nerve by surgery, which in itself did not lead to abnormal apoptosis of immune cells in mice, and the life span of the mice was no different from that of the sham operated mice, except that the level of norepinephrine in the spleen decreased.six weeks after surgery, the researchers injected lipopolysaccharide (LPS) into mice to stimulate immunity, and found a strange phenomenon.compared with normal mice, the germinal center (GC), which is the key structure of B cell development and maturation, did not change much in the mice with spleen nerve removed, but the number of spleen plasma cells (SPPC) capable of producing antibodies was significantly reduced! Obviously, the splenic nerve signal can promote immunity! When GC level was normal, SPPC significantly reduced the release of norepinephrine from splenic nerves.previously, scientists have discovered a T cell that can respond to norepinephrine and release acetylcholine, so the researchers speculate that the formation of plasma cells in the spleen may be affected by acetylcholine.of course, the researchers found a nicotine receptor containing α 9 subunit on the surface of B cells. Mice without α 9 nicotine receptor could not generate enough plasma cells under the stimulation of antigen, but the level of germinal center was normal.this suggests that activation of the splenic nerve promotes the formation of plasma cells from B cells through acetylcholine released by T cells.of course, this is not the end of the process. What nerve is in charge of all this? In order to trace the source, the researchers used fluorescent labeled pseudorabies virus (PRV) for retrograde tracking [2].96 hours after injection, the virus migrated upstream to the spinal cord, brainstem and hypothalamus, and obvious fluorescence appeared in the central amygdaloid nucleus (CEA) and hypothalamic paraventricular nucleus (PVN).it can be seen that the virus is enriched in CEA and pvncea, which is responsible for handling the physiological and behavioral responses related to threat and fear [3], while PVN regulates the hypothalamic pituitary adrenaline (HPA) axis response to external pressure [4].these two brain regions are also rich in neurons that produce corticotropin releasing hormone (CRH) [5].that's a little strange.we know that the activation of CRH neurons can lead to a large release of glucocorticoid from the adrenal gland, which inhibits immunity, which is the opposite of the immune enhancement observed in the study. therefore, it is safe to speculate that in addition to the known HPA axis, CRH neurons may also directly manipulate the splenic nerve and transmit immune enhancement signals! When the researchers used photogenetic methods to transform mice, the splenic nerve activation was observed after the CRH neurons were activated by light stimulation; moreover, the mice that used drugs to enhance the activity of CRH neurons also produced more splenic plasma cells after injection of antigens. after CRH neurons are activated, the increase of splenic nerve signal can be observed. Drug activated CRH neurons promote SPPC production. As we mentioned earlier, the neural activities in CEA and PVN are responsive to the external environment. Can we use this to create an environment that can enhance immune response? Considering that CRH neurons inhibit immunity at the hormonal level and promote immunity at the neural level, it is obvious that not all external stimuli can achieve the desired effect. the researchers designed a method called "isolated platform standing", in which mice were placed on a circular platform 1.5m above the ground and 10cm in diameter, so as to give the mice an appropriate but not exciting stimulation. mice are obviously afraid of heights. On the 8th to 12th day after injection of antigen, the number of plasma cells can be significantly increased by standing on this table for two 3 minutes every day. two weeks later, the IgG level of the mice was 70% higher than that of the control group! The researchers also tested another commonly used binding model (PPR). the stimulation to mice is obviously too strong, the cortisol level of mice is significantly increased, the glucocorticoid level is increased, and the immunity is suppressed. to sum up, the external environment can activate CRH neurons in CEA and PVN, CRH neurons can directly activate spleen nerve, activate T cells to release acetylcholine through norepinephrine, and acetylcholine acts on B cell surface receptors to promote plasma cell differentiation and antibody secretion after antigen stimulation! Professor Qi Hai, one of the corresponding authors of the mechanism map, believes that this may explain why moderate exercise can enhance immunity, but it is more likely to catch a cold after running a marathon - the appropriate stimulation of CRH neurons can enhance immunity, which is masked by immunosuppression caused by excessive stress. 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