ArticleImmunity2025
Sialylated IgG induces the transcription factor REST in alveolar macrophages to protect against lung inflammation and severe influenza disease.
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Article in Immunity, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed.
- Subclinical exposure to Streptococcus pyogenes drives the development of long-lived homologous immunity.Nature communications · 2026Article
- Inhibiting glycan degradation prevents HIV-induced inflammaging and cognitive impairment.Med (New York, N.Y.) · 2026Article
- Article
- Immunoglobulin G in aging and cancer.Frontiers in immunology · 2026Review
- More Than Just Antinuclear Antibodies: IgG Sialylation May Tip the Balance in Autoimmunity.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Antibody glycosylation in neuroimmune diseases.Journal of translational medicine · 2025Review
- ESAT-6 and CFP-10 reactive IgG in patients with tuberculosis inhibits intracellular bacteria.Cell reports · 2025Article
- Inhibiting Glycan Degradation Prevents HIV-Induced Inflammaging and Cognitive Impairment.bioRxiv : the preprint server for biology · 2025Article
- GWAS Reveals Key Candidate Genes Associated with Milk-Production in Saanen Goats.Animals : an open access journal from MDPI · 2025Article
- The anti-inflammatory activity of IgG is enhanced by co-engagement of type I and II Fc receptors.Science (New York, N.Y.) · 2025Article
- Estrogen Modulation of B Cell Immunity: Implications for HIV Control and Therapeutic Strategies.Comprehensive physiology · 2025Review
- Impact of age and prior COVID-19 on the response to influenza a components in the 2020-2021 Fluzone vaccine.Vaccine · 2025Article
- Mucosal immunotherapy targeting APC in lung disease.Journal of inflammation (London, England) · 2025Review
- Soluble Factors and Mechanisms Regulated by Sialylated IgG Signaling.Immunological reviews · 2025Review
- REST Is Restless in Neuronal and Non-Neuronal Virus Infections: An In Silico Analysis-Based Perspective.Viruses · 2025Review
- Immunoglobulin: unraveling its complex web in aging.Frontiers in immunology · 2025Review
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Authors and funding
23 authors.
Saborni ChakrabortyInstitute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
Bowie Yik-Ling ChengInstitute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
Desmond L EdwardsInstitute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Joseph C GonzalezInstitute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
David Kung-Chun ChiuDepartment of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Hong ZhengInstitute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
Courtney ScallanInstitute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
Xinrong GuoInstitute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
Gene S TanJ. Craig Venter Institute, La Jolla, San Diego, CA 92037, USA; Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, San Diego, CA 92037, USA.
Greg P CoffeyNuvig Therapeutics Inc., Redwood City, CA 94061, USA.
Pamela B ConleyNuvig Therapeutics Inc., Redwood City, CA 94061, USA.
Patrick S HumeDepartment of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, National Jewish Health, Denver, CO 80206, USA.
William J JanssenDepartment of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, National Jewish Health, Denver, CO 80206, USA.
Derek E ByersDepartment of Medicine, Division of Pulmonology and Critical Care Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
Philip A MuddDepartment of Emergency Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA; Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
Jeffery TaubenbergerViral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA.
Matthew MemoliLID Clinical Studies Unit, Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA.
Mark M DavisInstitute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; HHMI, Stanford University School of Medicine, Stanford, CA 94305, USA.
Katrin F ChuaDepartment of Medicine, Division of Endocrinology, Gerontology, and Metabolism, Stanford University School of Medicine, Stanford, CA 94305, USA; Geriatric Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
Michael S DiamondDepartment of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA; Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
Evangelos AndreakosLaboratory of Immunobiology, Center for Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Purvesh KhatriInstitute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Center for Biomedical Informatics Research, Stanford University School of Medicine, Stanford, CA 94305, USA.
Taia T WangInstitute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Infectious Diseases, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: taiawang@stanford.edu.
Funding
COLLABORATIVE INFLUENZA VACCINE INNOVATION CENTER: UNIVERSAL INFLUENZA VACCINE RESEARCH75N93019C00051 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KRAMMER, FLORIAN · 2019 to 2025
$105.4MUsing a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.U19AI057229 · NIAID · STANFORD UNIVERSITY · PI Mark Morris Davis · 2003 to 2026
$88.5MHousehold Respiratory Virus SARS-CoV-2 Transmission and Immunity Sub-Study (HRTS)U01AI144616 · NIAID · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI GORDON, AUBREE L, THOMAS, PAUL G. · 2019 to 2025
$43.7MDeveloping, Demonstrating, and Disseminating Innovative Programs to Achieve Translational SuccessUL1TR001866 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY, KRUEGER, JAMES G · 2016 to 2025
$40.6MMOLECULAR &CELLULAR IMMUNOBIOLOGYT32AI007290 · NIAID · STANFORD UNIVERSITY · PI Sean Curtis Bendall, Olivia M Martinez · 1985 to 2026
$27.0MThe effects of immune-age on immune-response and the molecular mechanisms which drive itP01AI153559 · NIAID · STANFORD UNIVERSITY · PI DAVIS, MARK MORRIS · 2021 to 2025
$17.8MInstitutional Career Development CoreKL2TR001865 · NCATS · ROCKEFELLER UNIVERSITY · PI SCHLESINGER, SARAH JANE · 2016 to 2025
$8.7MLung Macrophage Programming in Acute Lung InjuryR35HL140039 · NHLBI · NATIONAL JEWISH HEALTH · PI JANSSEN, WILLIAM · 2018 to 2024
$6.4MRegulation Of Lung Immunity By Antibody GlycosylationR01AI178298 · NIAID · STANFORD UNIVERSITY · PI Michael S Diamond, Taia Wang · 2024 to 2026
$2.7MA new mechanism of antiviral activity of 2’-5’ Oligoadenylate Synthetase 1R01AI150214 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DIAMOND, MICHAEL S, SARKAR, SAUMENDRA N · 2020 to 2024
$2.6MUnraveling Human T Follicular Helper Cell DevelopmentR01AI173203 · NIAID · WASHINGTON UNIVERSITY · PI Philip A Mudd · 2023 to 2026
$2.5MHistone Deacetylation Signaling in Aging and Cancer PathwaysR01CA268925 · NCI · PALO ALTO VETERANS INSTIT FOR RESEARCH · PI CHUA, KATRIN F. · 2021 to 2025
$2.4MBLRD VA IK6 BX006035NCATS NIH HHS KL2 TR001865NCATS NIH HHS UL1 TR001866NCI NIH HHS R01 CA268925NHLBI NIH HHS K08 HL155894NHLBI NIH HHS R35 HL140039NIAID NIH HHS 75N93019C00051NIAID NIH HHS P01 AI153559NIAID NIH HHS R01 AI150214NIAID NIH HHS R01 AI173203NIAID NIH HHS R01 AI178298NIAID NIH HHS T32 AI007290NIAID NIH HHS U01 AI144616NIAID NIH HHS U19 AI057229
Abstract
While most respiratory viral infections resolve with little harm to the host, severe symptoms arise when infection triggers an aberrant inflammatory response that damages lung tissue. Host regulators of virally induced lung inflammation have not been well defined. Here, we show that enrichment for sialylated, but not asialylated immunoglobulin G (IgG), predicted mild influenza disease in humans and was broadly protective against heterologous influenza viruses in a murine challenge model. Mechanistic studies show that sialylated IgG mediated this protection by inducing the transcription factor repressor element-1 silencing transcription factor (REST), which repressed nuclear factor κB (NF-κB)-driven responses, preventing severe lung inflammation and protecting lung function during influenza infection. Therapeutic administration of a recombinant, sialylated Fc molecule in clinical development similarly activated REST and protected against severe influenza disease, demonstrating that this pathway could be clinically harnessed. Overall, induction of REST through sialylated IgG signaling is a strategy to limit inflammatory disease sequelae in infections caused by antigenically distinct influenza strains.
Indexed as
Immunoglobulin GInfluenza, HumanMacrophages, AlveolarOrthomyxoviridae InfectionsPneumoniaRepressor ProteinsAnimalsDisease Models, AnimalFemaleHumansLungMiceMice, Inbred C57BLNF-kappa BRE1-Silencing Transcription FactorImmunoglobulin GNF-kappa BRE1-Silencing Transcription FactorRepressor Proteinsairway inflammationalveolar macrophageantibody signalingCD209IgG glycosylationIgG sialylationinfluenza immunityRE1-silencing transcription factorREST
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