Nature: promote IL-17A to produce behavioral symptoms that are expected to improve autism

December 25, 2019 / BIOON / - -- over the years, some parents have noticed that their autistic children's behavioral symptoms have abated with fever In the past 15 years, at least two large-scale studies have documented this phenomenon, but it is not clear why fever has this effect In a new study, researchers from the Massachusetts Institute of technology and Harvard Medical School in the United States revealed the possible cellular mechanism behind this phenomenon In the study of mice, they found that in some cases of infection, an immune molecule called IL-17A was released and inhibited a small part of the cerebral cortex, which had been previously found to be related to social behavior defects in mice The related research results were recently published in the journal Nature The title of the paper is "IL-17A promotes social in mouse models of neurodevelpmental disorders" The corresponding authors are Gloria Choi, assistant professor of brain and cognitive science at MIT, and Jun huh, assistant professor of immunology at Harvard Medical School The first author of this paper is Michael Douglas reed, a graduate student of MIT, and Yeong Shin Yim, a postdoctoral researcher of MIT Picture from nature, 2019, DOI: 10.1038/s41586-019-1843-6 "It's hard to understand that people have observed this phenomenon [in people with autism], I think it's because we don't know the mechanism," Choi said Now, this field, including my lab, is trying to prove how it works, from immune cells and molecules to receptors in the brain, and how these interactions lead to behavioral changes " While findings in mice may not always translate into treatments for humans, Choi said the study may help guide the development of strategies to help alleviate behavioral symptoms of autism or other neurological disorders Immune effects Choi and huh have previously explored other links between inflammation and autism In 2016, they found that mice born to mothers who were severely infected during pregnancy were more likely to show behavioral symptoms such as decreased social skills, repetitive behavior, and abnormal communication They found that this was caused by exposure to maternal IL-17A, which causes defects in certain brain regions of developing embryos This brain area, called primary somatosensory cortex dysgranular zone (s1dz), is a part of somatosensory cortex, which is considered to be responsible for sensing the position of human body in space "Immune activation in the mother leads to very specific cortical defects that lead to abnormal behavior in the offspring," Choi said The link between infection during pregnancy and autism in children has also been found in humans A 2010 study of all children born in Denmark between 1980 and 2005 found that severe viral infections in the first three months of pregnancy tripled the risk of autism in children, while severe bacterial infections in the second three months of pregnancy were associated with a 1.42-fold increase in the risk of autism These include influenza, viral gastroenteritis and severe urinary tract infections In the new study, Choi and huh turned their attention to the often reported link between fever and reduced autism symptoms "We would like to know if we can reproduce this phenomenon using a mouse model of neurodevelopmental disorders," Choi said Once this phenomenon is observed in animals, the mechanism can be explored " The researchers first looked at mice exposed to inflammation during pregnancy that showed behavioral symptoms They injected the mice with a bacterial component called lipopolysaccharide (LPS), which causes a fever response, and found that their social interaction temporarily returned to normal Further experiments showed that in the process of inflammation, these mice produced IL-17A, and IL-17A was bound to the receptor in s1dz, which was the brain area initially affected by maternal inflammation IL-17A reduced neural activity in s1dz, which temporarily made these mice more interested in social interaction with other mice If the researchers suppressed IL-17A or knocked out the IL-17A receptor, the reversal would not occur They also found that simply increasing the body temperature of these mice did not have any effect on behavior, which further confirmed that IL-17A was necessary to reverse behavioral symptoms "This shows that the immune system uses molecules like IL-17A to talk directly to the brain, and it can actually act like a neuromodulator, causing these behavioral changes," Choi said Our study provides another example of how the immune system regulates the brain " Dan Littman, Professor of immunology at New York University (not involved in the new study), said, "the great thing about this paper is that it shows that this effect on behavior is not necessarily the result of fever, but the result of cytokines produced There is increasing evidence that, at least in mammals, the central nervous system depends to some extent on cytokine signals during development or at different stages after birth " The researchers then did the same experiment in three other mouse models of neurological disease These mice lacked genes associated with autism and similar diseases - Shank3, cntnap2, or FMR1 The social behaviors of these mice were similar to those of mice exposed to inflammation in the womb, even though their symptom origins were different Injection of lipopolysaccharide into these mice did produce inflammation, but had no effect on their behavior The researchers found that in these mice, inflammation did not stimulate the production of IL-17A But if they injected the mice with IL-17A, their behavioral symptoms did improve This suggests that mice exposed to inflammation during pregnancy will eventually somehow make their immune system more likely to produce IL-17A in subsequent infections Choi and huh have previously found that the presence of certain bacteria in the gut can also trigger the IL-17A response They are now investigating whether the same bacteria present in the gut cause the reversal of the symptoms of lipopolysaccharide induced social behavior they found in this new study "It's amazing that finding the same immune molecule - IL-17A - can have the opposite effect in different situations: it promotes autism like behavior when used as a developing fetal brain; it improves autism like behavior when regulating neural activity in the brain of adult mice," huh said That's the complexity we're trying to understand " Choi lab is also investigating whether any immune molecules other than IL-17A affect brain and behavior "What's fascinating about this kind of communication is that the immune system sends its messenger molecules directly to the brain, where they act like brain molecules, changing the way neural circuits work and how behaviors are formed," Choi said (BIOON Com) reference: 1 Michael Douglas reed et al IL-17A promotions society in mouse models of neurodegenerative disorders Nature, 2019, DOI: 10.1038/s41586-019-1843-6 2 Study may explain how influences reduce authentication symptoms https://mediaexpress.com/news/2019-12-influences-authentication-symptoms.html