ArticleNature communications2018
Act1 is a negative regulator in T and B cells via direct inhibition of STAT3.
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Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
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25citing papers in PubMed, 2 pooled it
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Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 50 citations in OpenAlex.
- GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets.Nature communications · 2025Pooled it
- Advances in Pathogenesis of Sjögren's Syndrome.Journal of immunology research · 2021Pooled it
- The skin microbiota drives cutaneous immune checkpoint inhibitor toxicity in genetically susceptible mice.Cell host & microbe · 2026Article
- Therapeutic expansion of JAK inhibitors in Chinese dermatological practice: beyond atopic dermatitis to novel autoimmune frontiers.Frontiers in medicine · 2026Review
- Frequency of TNFalpha, IL17RA, and Act1 Genetic Polymorphisms in a Population with Psoriasis Compared with Healthy Individuals: Results in a Multiracial Population in Rio de Janeiro, Brazil.Acta dermato-venereologica · 2025Article
- Act1 drives chemoresistance via regulation of antioxidant RNA metabolism and redox homeostasis.The Journal of experimental medicine · 2024Article
- Synergistic effects of BTN3A1, SHP2, CD274, and STAT3 gene polymorphisms on the risk of systemic lupus erythematosus: a multifactorial dimensional reduction analysis.Clinical rheumatology · 2024Article
- Advances in cellular and molecular pathways of salivary gland damage in Sjögren's syndrome.Frontiers in immunology · 2024Review
- Lessons from Animal Models in Sjögren's Syndrome.International journal of molecular sciences · 2023Review
- NF-κB Activator 1 downregulation in macrophages activates STAT3 to promote adenoma-adenocarcinoma transition and immunosuppression in colorectal cancer.BMC medicine · 2023Article
- IL-17: Balancing Protective Immunity and Pathogenesis.Journal of immunology research · 2023Review
- Transgenic dry eye mouse models: powerful tools to study dry eye disease.International journal of ophthalmology · 2022Review
- A Mechanistic Insight into the Pathogenic Role of Interleukin 17A in Systemic Autoimmune Diseases.Mediators of inflammation · 2022Review
- Strategies of Targeting Inflammasome in the Treatment of Systemic Lupus Erythematosus.Frontiers in immunology · 2022Review
- CD5 Controls Gut Immunity by Shaping the Cytokine Profile of Intestinal T Cells.Frontiers in immunology · 2022Article
- Polygenic autoimmune disease risk alleles impacting B cell tolerance act in concert across shared molecular networks in mouse and in humans.Frontiers in immunology · 2022Review
- MicroRNA-146a-5p enhances T helper 17 cell differentiation via decreasing a disintegrin and metalloprotease 17 level in primary sjögren's syndrome.Bioengineered · 2021Article
- Licochalcone A improves the cognitive ability of mice by regulating T- and B-cell proliferation.Aging · 2021Article
- Cytokines that Modulate the Differentiation of Th17 Cells in Autoimmune Uveitis.Journal of immunology research · 2021Review
- Downregulation of Macrophage-Specific Act-1 Intensifies Periodontitis and Alveolar Bone Loss Possibly via TNF/NF-κB Signaling.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
24 authors at 10 institutions in 3 countries.
Cun-Jin ZhangDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44106, USA.
Chenhui WangDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44106, USA.
Meiling JiangDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44106, USA.
Chunfang GuDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44106, USA.
Jianxin XiaoDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44106, USA.
Xing ChenDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44106, USA.
Bradley N MartinDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44106, USA.
Fangqiang TangDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44106, USA.
Erin YamamotoDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44106, USA.
Yibo XianDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44106, USA.
Han WangDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44106, USA.
Fengling LiNational Gnotobiotic Rodent Resource Center, Department of Medicine and Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, 27599, USA.
R Balfour SartorNational Gnotobiotic Rodent Resource Center, Department of Medicine and Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, 27599, USA.
Howard SmithDepartment of Rheumatologic and Immunologic Disease, Cleveland Clinic, Cleveland, OH, 44106, USA.
M Elaine HusniDepartment of Rheumatologic and Immunologic Disease, Cleveland Clinic, Cleveland, OH, 44106, USA.
Fu-Dong ShiDepartment of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300051, China.
Ji GaoDiscovery Biology, Bristol-Myers Squibb, Princeton, NJ, 08540, USA.
Julie CarmanDiscovery Biology, Bristol-Myers Squibb, Princeton, NJ, 08540, USA.
Ashok DongreDiscovery Biology, Bristol-Myers Squibb, Princeton, NJ, 08540, USA.
Susan C McKarnsDepartment of Surgery, University of Missouri School of Medicine, Columbia, MO, 65212, USA.
Ken CoppietersType 1 Diabetes Center, Novo Nordisk A/S, Søborg, 2860, Denmark.
Trine N JørgensenDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44106, USA.
Warren J LeonardLaboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Xiaoxia LiDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44106, USA. lix@ccf.org.ORCID http://orcid.org/0000-0002-4872-9525
Cleveland Clinic Lerner College of Medicine · USBristol-Myers Squibb (United States) · USCleveland Clinic · USUniversity of North Carolina at Chapel Hill · USBarrow Neurological Institute · USCapital Medical University · CNChinese Academy of Medical Sciences & Peking Union Medical College · CNNational Institutes of Health · USNovo Nordisk (Denmark) · DKUniversity of Missouri · US
Funding
Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5MTELOMERASE INACTIVATION BY RNASE L SIGNALS CELL DEATHP01CA062220 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI LI, XIAOXIA, STARK, GEORGE ROBERT · 1994 to 2020
$35.6MMEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4MVascular Cell function and AtherosclerosisP01HL029582 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI FOX, PAUL L · 1985 to 2019
$32.0MPILOT AND FEASIBILITY STUDIESP30DK034987 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ROBERT S. SANDLER · 1985 to 2026
$30.5MIL-2 Family Cytokines and their Receptors-- Biology of the IL-21 systemZIAHL005408 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI LEONARD, WARREN J · 2009 to 2025
$23.7MRole of IL-10 in APC Regulation of Protective vs. Pathogenic T Cell Responses toP01DK094779 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SHEIKH, SHEHZAD Z. · 2013 to 2023
$17.9MNational Gnotobiotic Rodent Resource CenterP40OD010995 · OD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Ryan B Sartor · 2012 to 2026
$9.7MClinical and Translational Science Collaborative of ClevelandTL1TR000441 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$2.8MIRAKM and Mincle in ALDR01AA023722 · NIAAA · CLEVELAND CLINIC LERNER COM-CWRU · PI LI, XIAOXIA, NAGY, LAURA E. · 2015 to 2019
$2.2MMolecular and Cellular Mechanisms of IL-17 SignalingR01NS071996 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI LI, XIAOXIA · 2011 to 2015
$1.9MAhR and Regulatory T cellsR01ES022966 · NIEHS · UNIVERSITY OF MISSOURI-COLUMBIA · PI MCKARNS, SUSAN C · 2014 to 2018
$1.7MNCATS NIH HHS TL1 TR000441NCI NIH HHS P01 CA062220NCI NIH HHS P30 CA016086NHLBI NIH HHS P01 HL029582NIAAA NIH HHS R01 AA023722NIDDK NIH HHS P01 DK094779NIDDK NIH HHS P30 DK034987NIEHS NIH HHS R01 ES022966NIGMS NIH HHS T32 GM007250NIH HHS P40 OD010995NINDS NIH HHS R01 NS071996
Abstract
Although Act1 (adaptor for IL-17 receptors) is necessary for IL-17-mediated inflammatory responses, Act1- (but not Il17ra-, Il17rc-, or Il17rb-) deficient mice develop spontaneous SLE- and Sjögren's-like diseases. Here, we show that Act1 functions as a negative regulator in T and B cells via direct inhibition of STAT3. Mass spectrometry analysis detected an Act1-STAT3 complex, deficiency of Act1 (but not Il17ra-, Il17rc-, or Il17rb) results in hyper IL-23- and IL-21-induced STAT3 activation in T and B cells, respectively. IL-23R deletion or blockade of IL-21 ameliorates SLE- and Sjögren's-like diseases in Act1
Indexed as
Adaptor Proteins, Signal TransducingAnimalsAntibodies, MonoclonalB-LymphocytesCell DifferentiationDisease Models, AnimalFemaleGene Expression RegulationInterleukin-17Interleukin-21InterleukinsLeukocytes, MononuclearLupus Erythematosus, SystemicMiceMice, Inbred C57BLMice, KnockoutAdaptor Proteins, Signal TransducingAntibodies, MonoclonalIl17a protein, mouseIl17ra protein, mouseIl17rb protein, mouseIl17rc protein, mouseInterleukin-17Interleukin-21interleukin-23 receptor, mouseInterleukinsReceptors, InterleukinReceptors, Interleukin-17Stat3 protein, mouseSTAT3 Transcription FactorTraf3ip2 protein, mouse
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