Jonathan J. Carver, Wyatt P. Bunner, Rachael R. Denbrock, Changhong Yin, Weihua Huang, Erzsebet M. Szatmari, Alessandro Didonna
{"title":"ADAP1/CentA1缺失可预防自身免疫性脱髓鞘","authors":"Jonathan J. Carver, Wyatt P. Bunner, Rachael R. Denbrock, Changhong Yin, Weihua Huang, Erzsebet M. Szatmari, Alessandro Didonna","doi":"10.1096/fj.202403078R","DOIUrl":null,"url":null,"abstract":"<p>ArfGAP with dual PH domain-containing protein 1 (ADAP1), also known as Centaurin alpha-1 (CentA1), is an actin-binding protein highly expressed in the central nervous system (CNS) that was previously shown to regulate dendritic spine density and plasticity. In the context of disease, ADAP1/CentA1 has been linked to Alzheimer's disease (AD) pathogenesis, cancer progression, and human immunodeficiency virus (HIV) reactivation. Here, we document that ADAP1/CentA1 is also mechanistically involved in CNS autoimmunity. We show that ADAP1/CentA1 deficient mice exhibit partial resistance to developing experimental autoimmune encephalomyelitis (EAE), an in vivo disease model recapitulating several features of multiple sclerosis (MS) pathogenesis. MS is a chronic autoimmune disorder of the CNS characterized by focal immune cell infiltration, demyelination, and axonal injury. Its etiology is still elusive, but genetic and environmental factors contribute to disease risk. By combining detailed immunophenotyping and single-cell RNA sequencing (scRNA-seq), we demonstrate that ADAP1/CentA1 is necessary for mounting a sufficient autoimmune response for EAE initiation and progression. In particular, the current study highlights that ADAP1/CentA1 expression in the immune system mainly targets the functioning of regulatory T cells (Tregs), monocytes, and natural killer (NK) cells. In summary, our study defines a novel function for ADAP/CentA1 outside of the CNS and helps elucidate the early molecular events taking place in the peripheral immune system in response to encephalitogenic challenges.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 9","pages":""},"PeriodicalIF":4.2000,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202403078R","citationCount":"0","resultStr":"{\"title\":\"Loss of ADAP1/CentA1 Protects Against Autoimmune Demyelination\",\"authors\":\"Jonathan J. Carver, Wyatt P. Bunner, Rachael R. Denbrock, Changhong Yin, Weihua Huang, Erzsebet M. Szatmari, Alessandro Didonna\",\"doi\":\"10.1096/fj.202403078R\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>ArfGAP with dual PH domain-containing protein 1 (ADAP1), also known as Centaurin alpha-1 (CentA1), is an actin-binding protein highly expressed in the central nervous system (CNS) that was previously shown to regulate dendritic spine density and plasticity. In the context of disease, ADAP1/CentA1 has been linked to Alzheimer's disease (AD) pathogenesis, cancer progression, and human immunodeficiency virus (HIV) reactivation. Here, we document that ADAP1/CentA1 is also mechanistically involved in CNS autoimmunity. We show that ADAP1/CentA1 deficient mice exhibit partial resistance to developing experimental autoimmune encephalomyelitis (EAE), an in vivo disease model recapitulating several features of multiple sclerosis (MS) pathogenesis. MS is a chronic autoimmune disorder of the CNS characterized by focal immune cell infiltration, demyelination, and axonal injury. Its etiology is still elusive, but genetic and environmental factors contribute to disease risk. By combining detailed immunophenotyping and single-cell RNA sequencing (scRNA-seq), we demonstrate that ADAP1/CentA1 is necessary for mounting a sufficient autoimmune response for EAE initiation and progression. In particular, the current study highlights that ADAP1/CentA1 expression in the immune system mainly targets the functioning of regulatory T cells (Tregs), monocytes, and natural killer (NK) cells. In summary, our study defines a novel function for ADAP/CentA1 outside of the CNS and helps elucidate the early molecular events taking place in the peripheral immune system in response to encephalitogenic challenges.</p>\",\"PeriodicalId\":50455,\"journal\":{\"name\":\"The FASEB Journal\",\"volume\":\"39 9\",\"pages\":\"\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2025-05-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202403078R\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The FASEB Journal\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202403078R\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The FASEB Journal","FirstCategoryId":"99","ListUrlMain":"https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202403078R","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Loss of ADAP1/CentA1 Protects Against Autoimmune Demyelination
ArfGAP with dual PH domain-containing protein 1 (ADAP1), also known as Centaurin alpha-1 (CentA1), is an actin-binding protein highly expressed in the central nervous system (CNS) that was previously shown to regulate dendritic spine density and plasticity. In the context of disease, ADAP1/CentA1 has been linked to Alzheimer's disease (AD) pathogenesis, cancer progression, and human immunodeficiency virus (HIV) reactivation. Here, we document that ADAP1/CentA1 is also mechanistically involved in CNS autoimmunity. We show that ADAP1/CentA1 deficient mice exhibit partial resistance to developing experimental autoimmune encephalomyelitis (EAE), an in vivo disease model recapitulating several features of multiple sclerosis (MS) pathogenesis. MS is a chronic autoimmune disorder of the CNS characterized by focal immune cell infiltration, demyelination, and axonal injury. Its etiology is still elusive, but genetic and environmental factors contribute to disease risk. By combining detailed immunophenotyping and single-cell RNA sequencing (scRNA-seq), we demonstrate that ADAP1/CentA1 is necessary for mounting a sufficient autoimmune response for EAE initiation and progression. In particular, the current study highlights that ADAP1/CentA1 expression in the immune system mainly targets the functioning of regulatory T cells (Tregs), monocytes, and natural killer (NK) cells. In summary, our study defines a novel function for ADAP/CentA1 outside of the CNS and helps elucidate the early molecular events taking place in the peripheral immune system in response to encephalitogenic challenges.
期刊介绍:
The FASEB Journal publishes international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research. In addition to research, review, and hypothesis submissions, The FASEB Journal also seeks perspectives, commentaries, book reviews, and similar content related to the life sciences in its Up Front section.