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  1. Article ; Online: Variation in the basal immune state and implications for disease.

    Souquette, Aisha / Thomas, Paul G

    eLife

    2024  Volume 13

    Abstract: Analysis of pre-existing immunity and its effects on acute infection often focus on memory responses associated with a prior infectious exposure. However, memory responses occur in the context of the overall immune state and leukocytes must interact with ...

    Abstract Analysis of pre-existing immunity and its effects on acute infection often focus on memory responses associated with a prior infectious exposure. However, memory responses occur in the context of the overall immune state and leukocytes must interact with their microenvironment and other immune cells. Thus, it is important to also consider non-antigen-specific factors which shape the composite basal state and functional capacity of the immune system, termed here as I
    MeSH term(s) Humans ; Orthomyxoviridae Infections ; Orthomyxoviridae ; Influenza, Human ; Antibodies, Viral
    Chemical Substances Antibodies, Viral
    Language English
    Publishing date 2024-01-26
    Publishing country England
    Document type Review ; Journal Article
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.90091
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  2. Article ; Online: Principles and therapeutic applications of adaptive immunity.

    Chi, Hongbo / Pepper, Marion / Thomas, Paul G

    Cell

    2024  Volume 187, Issue 9, Page(s) 2052–2078

    Abstract: Adaptive immunity provides protection against infectious and malignant diseases. These effects are mediated by lymphocytes that sense and respond with targeted precision to perturbations induced by pathogens and tissue damage. Here, we review key ... ...

    Abstract Adaptive immunity provides protection against infectious and malignant diseases. These effects are mediated by lymphocytes that sense and respond with targeted precision to perturbations induced by pathogens and tissue damage. Here, we review key principles underlying adaptive immunity orchestrated by distinct T cell and B cell populations and their extensions to disease therapies. We discuss the intracellular and intercellular processes shaping antigen specificity and recognition in immune activation and lymphocyte functions in mediating effector and memory responses. We also describe how lymphocytes balance protective immunity against autoimmunity and immunopathology, including during immune tolerance, response to chronic antigen stimulation, and adaptation to non-lymphoid tissues in coordinating tissue immunity and homeostasis. Finally, we discuss extracellular signals and cell-intrinsic programs underpinning adaptive immunity and conclude by summarizing key advances in vaccination and engineering adaptive immune responses for therapeutic interventions. A deeper understanding of these principles holds promise for uncovering new means to improve human health.
    MeSH term(s) Humans ; Adaptive Immunity ; Animals ; B-Lymphocytes/immunology ; T-Lymphocytes/immunology ; Autoimmunity/immunology
    Language English
    Publishing date 2024-04-11
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2024.03.037
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  3. Article ; Online: (E1)levating COVID-19 vaccine efficiency with adenoviral E1 proteins.

    Green, Douglas R / Thomas, Paul G

    Science advances

    2022  Volume 8, Issue 34, Page(s) eade3956

    Abstract: Improved adenovirus-based COVID-19 vaccines provide an important tool to combat the ever-evolving virus. ...

    Abstract Improved adenovirus-based COVID-19 vaccines provide an important tool to combat the ever-evolving virus.
    Language English
    Publishing date 2022-08-24
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.ade3956
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  4. Article ; Online: Count on us: T cells in SARS-CoV-2 infection and vaccination.

    Kedzierska, Katherine / Thomas, Paul G

    Cell reports. Medicine

    2022  Volume 3, Issue 3, Page(s) 100562

    Abstract: Robust T cell responses have been associated with milder outcomes in many infections. T cells also establish long-term memory pools and, as they are predominantly directed toward epitopes encompassing conserved peptides, can respond to SARS-CoV-2 ... ...

    Abstract Robust T cell responses have been associated with milder outcomes in many infections. T cells also establish long-term memory pools and, as they are predominantly directed toward epitopes encompassing conserved peptides, can respond to SARS-CoV-2 variants, including Omicron. Here, we discuss epitope-specific CD8
    MeSH term(s) CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; COVID-19/prevention & control ; Epitopes ; Humans ; Immunologic Memory ; SARS-CoV-2 ; Vaccination
    Chemical Substances Epitopes
    Language English
    Publishing date 2022-02-25
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ISSN 2666-3791
    ISSN (online) 2666-3791
    DOI 10.1016/j.xcrm.2022.100562
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  5. Article ; Online: T

    Schattgen, Stefan A / Thomas, Paul G

    Science immunology

    2021  Volume 6, Issue 55

    Abstract: T resident helper cells ( ... ...

    Abstract T resident helper cells (T
    MeSH term(s) B-Lymphocytes ; T-Lymphocyte Subsets ; T-Lymphocytes, Helper-Inducer
    Language English
    Publishing date 2021-01-05
    Publishing country United States
    Document type Journal Article ; Review ; Comment
    ISSN 2470-9468
    ISSN (online) 2470-9468
    DOI 10.1126/sciimmunol.abf2886
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  6. Article ; Online: Human Susceptibility to Influenza Infection and Severe Disease.

    Mettelman, Robert C / Thomas, Paul G

    Cold Spring Harbor perspectives in medicine

    2021  Volume 11, Issue 5

    Abstract: Influenza viruses are a persistent threat to global human health. Increased susceptibility to infection and the risk factors associated with progression to severe influenza-related disease are determined by a multitude of viral, host, and environmental ... ...

    Abstract Influenza viruses are a persistent threat to global human health. Increased susceptibility to infection and the risk factors associated with progression to severe influenza-related disease are determined by a multitude of viral, host, and environmental conditions. Decades of epidemiologic research have broadly defined high-risk groups, while new genomic association studies have identified specific host factors impacting an individual's response to influenza. Here, we review and highlight both human susceptibility to influenza infection and the conditions that lead to severe influenza disease.
    MeSH term(s) Disease Susceptibility ; Host-Pathogen Interactions ; Humans ; Influenza, Human/physiopathology ; Patient Acuity
    Language English
    Publishing date 2021-05-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ISSN 2157-1422
    ISSN (online) 2157-1422
    DOI 10.1101/cshperspect.a038711
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  7. Article ; Online: Cutting-Edge Research in COVID-19 and General Viral Immunology.

    Thomas, Paul G / Kedzierska, Katherine

    Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research

    2021  Volume 41, Issue 12, Page(s) 477–481

    Language English
    Publishing date 2021-12-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1226675-9
    ISSN 1557-7465 ; 1079-9907
    ISSN (online) 1557-7465
    ISSN 1079-9907
    DOI 10.1089/jir.2021.29034.dpk
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    Zs.A 1748: Show issues Location:
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  8. Article ; Online: Pulmonary inflammation and fibroblast immunoregulation: from bench to bedside.

    Ghonim, Mohamed A / Boyd, David F / Flerlage, Tim / Thomas, Paul G

    The Journal of clinical investigation

    2023  Volume 133, Issue 17

    Abstract: In recent years, there has been an explosion of interest in how fibroblasts initiate, sustain, and resolve inflammation across disease states. Fibroblasts contain heterogeneous subsets with diverse functionality. The phenotypes of these populations vary ... ...

    Abstract In recent years, there has been an explosion of interest in how fibroblasts initiate, sustain, and resolve inflammation across disease states. Fibroblasts contain heterogeneous subsets with diverse functionality. The phenotypes of these populations vary depending on their spatial distribution within the tissue and the immunopathologic cues contributing to disease progression. In addition to their roles in structurally supporting organs and remodeling tissue, fibroblasts mediate critical interactions with diverse immune cells. These interactions have important implications for defining mechanisms of disease and identifying potential therapeutic targets. Fibroblasts in the respiratory tract, in particular, determine the severity and outcome of numerous acute and chronic lung diseases, including asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, and idiopathic pulmonary fibrosis. Here, we review recent studies defining the spatiotemporal identity of the lung-derived fibroblasts and the mechanisms by which these subsets regulate immune responses to insult exposures and highlight past, current, and future therapeutic targets with relevance to fibroblast biology in the context of acute and chronic human respiratory diseases. This perspective highlights the importance of tissue context in defining fibroblast-immune crosstalk and paves the way for identifying therapeutic approaches to benefit patients with acute and chronic pulmonary disorders.
    MeSH term(s) Humans ; Pneumonia ; Inflammation ; Fibroblasts ; Asthma ; Pulmonary Disease, Chronic Obstructive
    Language English
    Publishing date 2023-09-01
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI170499
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  9. Article ; Online: Immunology of SARS-CoV-2 infection in children.

    Chou, Janet / Thomas, Paul G / Randolph, Adrienne G

    Nature immunology

    2022  Volume 23, Issue 2, Page(s) 177–185

    Abstract: Children and adolescents exhibit a broad range of clinical outcomes from SARS-CoV-2 infection, with the majority having minimal to mild symptoms. Additionally, some succumb to a severe hyperinflammatory post-infectious complication called multisystem ... ...

    Abstract Children and adolescents exhibit a broad range of clinical outcomes from SARS-CoV-2 infection, with the majority having minimal to mild symptoms. Additionally, some succumb to a severe hyperinflammatory post-infectious complication called multisystem inflammatory syndrome in children (MIS-C), predominantly affecting previously healthy individuals. Studies characterizing the immunological differences associated with these clinical outcomes have identified pathways important for host immunity to SARS-CoV-2 and innate modulators of disease severity. In this Review, we delineate the immunological mechanisms underlying the spectrum of pediatric immune response to SARS-CoV-2 infection in comparison with that of adults.
    MeSH term(s) Adolescent ; Adolescent Development ; Age Factors ; Asymptomatic Diseases ; COVID-19/complications ; COVID-19/diagnosis ; COVID-19/immunology ; COVID-19/virology ; Child ; Child Development ; Comorbidity ; Host-Pathogen Interactions ; Humans ; Immunity, Innate ; Risk Factors ; SARS-CoV-2/immunology ; SARS-CoV-2/pathogenicity ; Severity of Illness Index ; Systemic Inflammatory Response Syndrome/diagnosis ; Systemic Inflammatory Response Syndrome/immunology ; Systemic Inflammatory Response Syndrome/virology
    Language English
    Publishing date 2022-02-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-021-01123-9
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    Zs.A 5294: Show issues Location:
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  10. Article ; Online: Mucosal immune responses to infection and vaccination in the respiratory tract.

    Mettelman, Robert C / Allen, E Kaitlynn / Thomas, Paul G

    Immunity

    2022  Volume 55, Issue 5, Page(s) 749–780

    Abstract: The lungs are constantly exposed to inhaled debris, allergens, pollutants, commensal or pathogenic microorganisms, and respiratory viruses. As a result, innate and adaptive immune responses in the respiratory tract are tightly regulated and are in ... ...

    Abstract The lungs are constantly exposed to inhaled debris, allergens, pollutants, commensal or pathogenic microorganisms, and respiratory viruses. As a result, innate and adaptive immune responses in the respiratory tract are tightly regulated and are in continual flux between states of enhanced pathogen clearance, immune-modulation, and tissue repair. New single-cell-sequencing techniques are expanding our knowledge of airway cellular complexity and the nuanced connections between structural and immune cell compartments. Understanding these varied interactions is critical in treatment of human pulmonary disease and infections and in next-generation vaccine design. Here, we review the innate and adaptive immune responses in the lung and airways following infection and vaccination, with particular focus on influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The ongoing SARS-CoV-2 pandemic has put pulmonary research firmly into the global spotlight, challenging previously held notions of respiratory immunity and helping identify new populations at high risk for respiratory distress.
    MeSH term(s) COVID-19/prevention & control ; Humans ; Immunity, Innate ; Immunity, Mucosal ; Lung ; SARS-CoV-2 ; Vaccination
    Language English
    Publishing date 2022-05-24
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2022.04.013
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