Regulatory T(Treg) cells, a subtype of immunosuppressive CD4^+T cells, are vital for maintaining immune homeostasis in healthy people. Forkhead box protein P3(FOXP3), a member of the forkhead-wingedhelix family, is th...Regulatory T(Treg) cells, a subtype of immunosuppressive CD4^+T cells, are vital for maintaining immune homeostasis in healthy people. Forkhead box protein P3(FOXP3), a member of the forkhead-wingedhelix family, is the pivotal transcriptional factor of Treg cells. The expression, post-translational modifications, and protein complex of FOXP3 present a great impact on the functional stability and immune plasticity of Treg cells in vivo. In particular, the mutation of FOXP3 can result in immune dysregulation,polyendocrinopathy, enteropathy, X-linked(IPEX) syndrome, which is a rare genetic disease mostly diagnosed in early childhood and can soon be fatal. IPEX syndrome is related to several manifestations,including dermatitis, enteropathy, type 1 diabetes, thyroiditis, and so on. Here, we summarize some recent findings on FOXP3 regulation and Treg cell function. We also review the current knowledge about the underlying mechanism of FOXP3 mutant-induced IPEX syndrome and some latest clinical prospects.At last, this review offers a novel insight into the role played by the FOXP3 complex in potential therapeutic applications in IPEX syndrome.展开更多
Autism and autism spectrum disorders(ASD) refer to a range of conditions characterized by impaired social and communication skills and repetitive behaviors caused by different combinations of genetic and environmental...Autism and autism spectrum disorders(ASD) refer to a range of conditions characterized by impaired social and communication skills and repetitive behaviors caused by different combinations of genetic and environmental influences. Although the pathophysiology underlying ASD is still unclear, recent evidence suggests that immune dysregulation and neuroinflammation play a role in the etiology of ASD. In particular, there is direct evidence supporting a role for maternal immune activation during prenatal life in neurodevelopmental conditions. Currently, the available options of behavioral therapies and pharmacological and supportive nutritional treatments in ASD are only symptomatic. Given the disturbing rise in the incidence of ASD, and the fact that there is no effective pharmacological therapy for ASD, there is an urgent need for new therapeutic options. Mesenchymal stem cells(MSCs) possess immunomodulatory properties that make them relevant to several diseases associated with inflammation and tissue damage. The paracrine regenerative mechanisms of MSCs are also suggested to be therapeutically beneficial for ASD.Thus the underlying pathology in ASD, including immune system dysregulation and inflammation, represent potential targets for MSC therapy. This review willfocus on immune dysfunction in the pathogenesis of ASD and will further discuss the therapeutic potential for MSCs in mediating ASD-related immunological disorders.展开更多
基金supported by National Natural Science Foundation of China (grants: 81830051,31525008, 31670911 and 31961133011)Shanghai Academic Research Leader 16XD1403800+1 种基金Shanghai Jiao Tong University (SJTU)-The Chinese University of Hong Kong (CUHK) Joint Research Collaboration Fundthe Fundamental Research Funds for Central Universities.
文摘Regulatory T(Treg) cells, a subtype of immunosuppressive CD4^+T cells, are vital for maintaining immune homeostasis in healthy people. Forkhead box protein P3(FOXP3), a member of the forkhead-wingedhelix family, is the pivotal transcriptional factor of Treg cells. The expression, post-translational modifications, and protein complex of FOXP3 present a great impact on the functional stability and immune plasticity of Treg cells in vivo. In particular, the mutation of FOXP3 can result in immune dysregulation,polyendocrinopathy, enteropathy, X-linked(IPEX) syndrome, which is a rare genetic disease mostly diagnosed in early childhood and can soon be fatal. IPEX syndrome is related to several manifestations,including dermatitis, enteropathy, type 1 diabetes, thyroiditis, and so on. Here, we summarize some recent findings on FOXP3 regulation and Treg cell function. We also review the current knowledge about the underlying mechanism of FOXP3 mutant-induced IPEX syndrome and some latest clinical prospects.At last, this review offers a novel insight into the role played by the FOXP3 complex in potential therapeutic applications in IPEX syndrome.
基金Supported by National Nature Science Foundation of China,No.81660381
文摘Autism and autism spectrum disorders(ASD) refer to a range of conditions characterized by impaired social and communication skills and repetitive behaviors caused by different combinations of genetic and environmental influences. Although the pathophysiology underlying ASD is still unclear, recent evidence suggests that immune dysregulation and neuroinflammation play a role in the etiology of ASD. In particular, there is direct evidence supporting a role for maternal immune activation during prenatal life in neurodevelopmental conditions. Currently, the available options of behavioral therapies and pharmacological and supportive nutritional treatments in ASD are only symptomatic. Given the disturbing rise in the incidence of ASD, and the fact that there is no effective pharmacological therapy for ASD, there is an urgent need for new therapeutic options. Mesenchymal stem cells(MSCs) possess immunomodulatory properties that make them relevant to several diseases associated with inflammation and tissue damage. The paracrine regenerative mechanisms of MSCs are also suggested to be therapeutically beneficial for ASD.Thus the underlying pathology in ASD, including immune system dysregulation and inflammation, represent potential targets for MSC therapy. This review willfocus on immune dysfunction in the pathogenesis of ASD and will further discuss the therapeutic potential for MSCs in mediating ASD-related immunological disorders.
