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    Home > Active Ingredient News > Study of Nervous System > Nature Sub-Journal: Zhou Zikai's research group collaborates to propose potential treatment strategies for immune abnormal autism

    Nature Sub-Journal: Zhou Zikai's research group collaborates to propose potential treatment strategies for immune abnormal autism

    • Last Update: 2021-05-09
    • Source: Internet
    • Author: User
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    Autism spectrum disorder is a group of central nervous system developmental diseases with complex pathogenic mechanisms, highly heterogeneous etiology, and large unmet clinical needs.

    At present, the academic community is focusing on its genetic etiology and pathological mechanism, and it has been found that part of the occurrence of autism can be attributed to hundreds of genetic abnormalities, and there is a lack of universal targets to support the development of conventional drugs.

    The results of epidemiology and laboratory animal studies indicate that maternal immune activation (MIA) triggered by pathogens from the mother during pregnancy is an important risk factor for inducing neuropsychiatric diseases such as autism in offspring; MIA affects offspring’s peripheral and central nervous immune systems It can have a lasting effect, which may be the cause of some immune abnormal autism.

    Recently, Zhou Zikai, a researcher at the Shanghai Mental Health Center-Shanghai Institute of Materia Medica, Chinese Academy of Sciences, collaborated with Ji Minjun, a professor at the State Key Laboratory of Reproductive Medicine and Department of Pathogenic Biology, Nanjing Medical University, to publish a research paper Rescue online on Nature Neuroscience of maternal immune activation-induced behavioral abnormalities in adult mouse offspring by pathogen-activated maternal Treg cells.

    The study established a new disease animal model of MIA, revealed the mechanism by which MIA affects the immune system of offspring and caused autism-related phenotypes, and found that the autism phenotype can be improved by regulating the immune system of adult offspring mice .

    In the study, the Toxoplasma tachyzoite soluble antigen (STAg), which infects one third of the world’s population, was used to induce MIA, and a mouse model with immune abnormalities and autism phenotypes was established.

    Compared with the two chemicals commonly used in academia, the virus mimic poly(I:C) and the bacterial mimic LPS, the parasite mimic STAg is a complex antigen, which can more comprehensively induce abnormal immune lineage, especially it can effectively induce acquisition Sexual cellular immune response.

    Studies have shown that the offspring of sick rats have abnormal peripheral and central nervous immune spectrum until adulthood, and their CD4+ T cell spectrum is highly consistent with some autistic patients; sick rats have autistic cores with social interaction defects, repetitive stereotypes, and communication disorders Symptoms, and a marked anxiety phenotype.

    After adoptive Treg cell transfer therapy (Adoptive Treg cell transfer therapy) on adult sick mice, the study found that although the improvement of the abnormal microstructure of the white matter fibers of the sick mice was relatively limited, the treatment effectively reversed most of the Immunology and behavioral phenotypes.

    Through single-cell sequencing technology (scRNA-seq) to compare the transcriptomes of Treg cells from different sources, the study identified a group of high-efficiency Treg cell subsets and their transcriptomic characteristics.
    This type of high-efficiency Treg cells can better It works by moving into the brain area associated with disease symptoms.

    The research builds and conducts research on a new type of MIA disease animal model with autism phenotype, and proposes regulatory T cell drugs engineered according to the molecular characteristics of high-efficiency cell subsets, which are expected to improve the core symptoms of immune abnormal autism It provides new ideas for follow-up clinical translational research.

    Xu Zhipeng, associate professor of Nanjing Medical University, Zhang Xiaoyun, postdoctoral fellow at Shanghai Institute of Materia Medica, and Chang Hao, a doctoral student from Nanjing Medical University, are the co-authors of the paper, and Zhou Zikai and Ji Minjun are the co-corresponding authors of the paper.

    The research work was funded by the National Natural Science Foundation of China, the Shanghai Municipal Science and Technology Commission, the Natural Science Foundation of Jiangsu Province, and the Shanghai Mental Health Center.

    Toxoplasma gondii tachyzoite complex antigen (STAg) can effectively induce maternal immune activation (MIA) to produce offspring mice with high risk of disease.

    Compared with healthy offspring, offspring with autism phenotype (ASD offspring), the ratio of peripheral Th1/Th17 cell subsets is up-regulated.
    Astrocytes secrete large amounts of IL-6 factors in the brain.
    Brain dysfunction.

    Adoptive cell therapy is used to infuse peripheral Treg cells into the brain under the action of chemokine CCL22, and regulate neurological function through high expression of PD1, ICOS, IL-10 and other molecules to improve the autism-related phenotype of sick mice.

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