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  1. Article ; Online: IL-10 Family Cytokines IL-10 and IL-22: from Basic Science to Clinical Translation.

    Ouyang, Wenjun / O'Garra, Anne

    Immunity

    2019  Volume 50, Issue 4, Page(s) 871–891

    Abstract: Cytokines are among the most important effector and messenger molecules in the immune system. They profoundly participate in immune responses during infection and inflammation, protecting against or contributing to diseases such as allergy, autoimmunity, ...

    Abstract Cytokines are among the most important effector and messenger molecules in the immune system. They profoundly participate in immune responses during infection and inflammation, protecting against or contributing to diseases such as allergy, autoimmunity, and cancer. Manipulating cytokine pathways, therefore, is one of the most effective strategies to treat various diseases. IL-10 family cytokines exert essential functions to maintain tissue homeostasis during infection and inflammation through restriction of excessive inflammatory responses, upregulation of innate immunity, and promotion of tissue repairing mechanisms. Their important functions in diseases are supported by data from many preclinical models, human genetic studies, and clinical interventions. Despite significant efforts, however, there is still no clinically approved therapy through manipulating IL-10 family cytokines. Here, we summarize the recent progress in understanding the biology of this family of cytokines, suggesting more specific strategies to maneuver these cytokines for the effective treatment of inflammatory diseases and cancers.
    MeSH term(s) Animals ; Autoimmune Diseases/immunology ; Autoimmune Diseases/therapy ; Cytokines/classification ; Cytokines/genetics ; Gene Expression Regulation ; Humans ; Immunity, Innate ; Infections/immunology ; Infections/therapy ; Inflammation/immunology ; Inflammation/therapy ; Interleukin-10/genetics ; Interleukin-10/immunology ; Interleukins/genetics ; Interleukins/immunology ; Lymphocyte Subsets/immunology ; Mice ; Multigene Family ; Myeloid Cells/immunology ; Neoplasms/immunology ; Neoplasms/therapy ; Signal Transduction ; Transcription Factors/physiology ; Interleukin-22
    Chemical Substances Cytokines ; IL10 protein, human ; Interleukins ; Transcription Factors ; Interleukin-10 (130068-27-8)
    Language English
    Publishing date 2019-04-17
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2019.03.020
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  2. Article ; Online: Host-directed immunotherapy of viral and bacterial infections: past, present and future.

    Wallis, Robert S / O'Garra, Anne / Sher, Alan / Wack, Andreas

    Nature reviews. Immunology

    2022  Volume 23, Issue 2, Page(s) 121–133

    Abstract: The advent of COVID-19 and the persistent threat of infectious diseases such as tuberculosis, malaria, influenza and HIV/AIDS remind us of the marked impact that infections continue to have on public health. Some of the most effective protective measures ...

    Abstract The advent of COVID-19 and the persistent threat of infectious diseases such as tuberculosis, malaria, influenza and HIV/AIDS remind us of the marked impact that infections continue to have on public health. Some of the most effective protective measures are vaccines but these have been difficult to develop for some of these infectious diseases even after decades of research. The development of drugs and immunotherapies acting directly against the pathogen can be equally challenging, and such pathogen-directed therapeutics have the potential disadvantage of selecting for resistance. An alternative approach is provided by host-directed therapies, which interfere with host cellular processes required for pathogen survival or replication, or target the host immune response to infection (immunotherapies) to either augment immunity or ameliorate immunopathology. Here, we provide a historical perspective of host-directed immunotherapeutic interventions for viral and bacterial infections and then focus on SARS-CoV-2 and Mycobacterium tuberculosis, two major human pathogens of the current era, to indicate the key lessons learned and discuss candidate immunotherapeutic approaches, with a focus on drugs currently in clinical trials.
    MeSH term(s) Humans ; COVID-19/therapy ; SARS-CoV-2 ; Bacterial Infections/therapy ; Immunotherapy ; Communicable Diseases
    Language English
    Publishing date 2022-06-07
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Intramural
    ZDB-ID 2062776-2
    ISSN 1474-1741 ; 1474-1733
    ISSN (online) 1474-1741
    ISSN 1474-1733
    DOI 10.1038/s41577-022-00734-z
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  3. Article ; Online: Interferon-gamma release assay conversion after Mycobacterium tuberculosis exposure specifically associates with greater risk of progression to tuberculosis: A prospective cohort study in Leicester, UK.

    Kim, Jee Whang / Nazareth, Joshua / Lee, Joanne / Patel, Hemu / Woltmann, Gerrit / Verma, Raman / O'Garra, Anne / Haldar, Pranabashis

    International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases

    2024  Volume 141, Page(s) 106982

    Abstract: Objectives: We investigated whether quantifying the serial QuantiFERON-TB Gold (QFT) response improves tuberculosis (TB) risk stratification in pulmonary TB (PTB) contacts.: Methods: A total of 297 untreated adult household PTB contacts, QFT tested ... ...

    Abstract Objectives: We investigated whether quantifying the serial QuantiFERON-TB Gold (QFT) response improves tuberculosis (TB) risk stratification in pulmonary TB (PTB) contacts.
    Methods: A total of 297 untreated adult household PTB contacts, QFT tested at baseline and 3 months after index notification, were prospectively observed (median 1460 days). Normal variance of serial QFT responses was established in 46 extrapulmonary TB contacts. This informed categorisation of the response in QFT-positive PTB contacts as converters, persistently QFT-positive with significant increase (PP
    Results: In total, eight co-prevalent TB (disease ≤3 months after index notification) and 12 incident TB (>3 months after index notification) cases were diagnosed. Genetic linkage to the index strain was confirmed in all culture-positive progressors. The cumulative 2-year incident TB risk in QFT-positive contacts was 8.4% (95% confidence interval, 3.0-13.6%); stratifying by serial QFT response, significantly higher risk was observed in QFT converters (28%), compared with PP
    Conclusions: QFT conversion, rather than quantitative changes of a persistently positive serial QFT response, is associated with greater TB risk and exposure to rapidly progressive TB.
    MeSH term(s) Adult ; Humans ; Interferon-gamma Release Tests ; Mycobacterium tuberculosis/genetics ; Prospective Studies ; Tuberculin Test ; Tuberculosis/diagnosis ; Tuberculosis/epidemiology ; United Kingdom/epidemiology ; Latent Tuberculosis/diagnosis ; Latent Tuberculosis/epidemiology
    Language English
    Publishing date 2024-02-24
    Publishing country Canada
    Document type Journal Article
    ZDB-ID 1331197-9
    ISSN 1878-3511 ; 1201-9712
    ISSN (online) 1878-3511
    ISSN 1201-9712
    DOI 10.1016/j.ijid.2024.02.025
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  4. Article ; Online: Regulating the regulator: Bhlhe40 directly keeps IL-10 in check.

    Gabryšová, Leona / O'Garra, Anne

    The Journal of experimental medicine

    2018  Volume 215, Issue 7, Page(s) 1767–1769

    Abstract: In this issue ... ...

    Abstract In this issue of
    MeSH term(s) Humans ; Interleukin-10 ; Mycobacterium tuberculosis ; Tuberculosis
    Chemical Substances Interleukin-10 (130068-27-8)
    Language English
    Publishing date 2018-06-07
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20180824
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  5. Article: Transcriptomic analysis reveals diverse gene expression changes in airway macrophages during experimental allergic airway disease.

    Branchett, William J / O'Garra, Anne / Lloyd, Clare M

    Wellcome open research

    2020  Volume 5, Page(s) 101

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2020-06-22
    Publishing country England
    Document type Journal Article
    ISSN 2398-502X
    ISSN 2398-502X
    DOI 10.12688/wellcomeopenres.15875.2
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  6. Article: Blimp-1 and c-Maf regulate

    Cox, Luke S / Alvarez-Martinez, Marisol / Wu, Xuemei / Gabryšová, Leona / Luisier, Raphaëlle / Briscoe, James / Luscombe, Nicholas M / O'Garra, Anne

    Wellcome open research

    2023  Volume 8, Page(s) 403

    Abstract: Background: CD4 : Methods: We applied computational analysis of gene regulation derived from temporal profiling of gene expression clusters obtained from bulk RNA sequencing (RNA-seq) of flow cytometry sorted naïve CD4 : Results: We show that the ... ...

    Abstract Background: CD4
    Methods: We applied computational analysis of gene regulation derived from temporal profiling of gene expression clusters obtained from bulk RNA sequencing (RNA-seq) of flow cytometry sorted naïve CD4
    Results: We show that the transcription factors Blimp-1 and c-Maf each have unique and common effects on cytokine gene regulation and not only co-operate to induce
    Conclusions: These data show that Blimp-1 and c-Maf positively and negatively regulate a network of both unique and common anti-inflammatory and pro-inflammatory genes to reinforce a Th1 response in mice that will eradicate pathogens with minimum immunopathology.
    Language English
    Publishing date 2023-12-01
    Publishing country England
    Document type Journal Article
    ISSN 2398-502X
    ISSN 2398-502X
    DOI 10.12688/wellcomeopenres.19680.2
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  7. Article ; Online: Biology and therapeutic potential of interleukin-10.

    Saraiva, Margarida / Vieira, Paulo / O'Garra, Anne

    The Journal of experimental medicine

    2019  Volume 217, Issue 1

    Abstract: The cytokine IL-10 is a key anti-inflammatory mediator ensuring protection of a host from over-exuberant responses to pathogens and microbiota, while playing important roles in other settings as sterile wound healing, autoimmunity, cancer, and ... ...

    Abstract The cytokine IL-10 is a key anti-inflammatory mediator ensuring protection of a host from over-exuberant responses to pathogens and microbiota, while playing important roles in other settings as sterile wound healing, autoimmunity, cancer, and homeostasis. Here we discuss our current understanding of the regulation of IL-10 production and of the molecular pathways associated with IL-10 responses. In addition to IL-10's classic inhibitory effects on myeloid cells, we also describe the nonclassic roles attributed to this pleiotropic cytokine, including how IL-10 regulates basic processes of neural and adipose cells and how it promotes CD8 T cell activation, as well as epithelial repair. We further discuss its therapeutic potential in the context of different diseases and the outstanding questions that may help develop an effective application of IL-10 in diverse clinical settings.
    MeSH term(s) Animals ; Autoimmunity/immunology ; Cytokines/immunology ; Cytokines/metabolism ; Humans ; Inflammation/immunology ; Inflammation/metabolism ; Interleukin-10/immunology ; Interleukin-10/metabolism ; Neoplasms/immunology ; Neoplasms/metabolism
    Chemical Substances Cytokines ; Interleukin-10 (130068-27-8)
    Language English
    Publishing date 2019-10-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20190418
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  8. Article ; Online: Correction: Transcription Factors Directing Th2 Differentiation: Gata-3 Plays a Dominant Role.

    O'Garra, Anne / Gabryšová, Leona

    Journal of immunology (Baltimore, Md. : 1950)

    2016  Volume 197, Issue 11, Page(s) 4504

    Language English
    Publishing date 2016-12-01
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1601671
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  9. Article ; Online: Transcription Factors Directing Th2 Differentiation: Gata-3 Plays a Dominant Role.

    O'Garra, Anne / Gabryšová, Leona

    Journal of immunology (Baltimore, Md. : 1950)

    2016  Volume 196, Issue 11, Page(s) 4423–4425

    MeSH term(s) Cell Differentiation ; GATA3 Transcription Factor ; Humans ; Th2 Cells
    Chemical Substances GATA3 Transcription Factor
    Language English
    Publishing date 2016-05-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1600646
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  10. Article ; Online: Systems approach to understand the immune response in tuberculosis: an iterative process between mouse models and human disease.

    O'Garra, Anne

    Cold Spring Harbor symposia on quantitative biology

    2013  Volume 78, Page(s) 173–177

    Abstract: Tuberculosis remains a disease of considerable mortality and morbidity. The immune response determining whether individuals infected with the pathogen Mycobacterium tuberculosis control the infection, and remain latent, or go on to develop active ... ...

    Abstract Tuberculosis remains a disease of considerable mortality and morbidity. The immune response determining whether individuals infected with the pathogen Mycobacterium tuberculosis control the infection, and remain latent, or go on to develop active tuberculosis disease is poorly understood. Our studies used microarray technology to derive blood transcriptional profiles of the host response during tuberculosis, which, combined with data from experimental systems, highlighted a potentially detrimental role for Type I interferons during infection, with important implications for vaccine and therapeutic development. Our studies have also provided candidate biomarkers, which may advance diagnosis and treatment monitoring. These studies thus exemplify the promise of a systems biology approach to understand the immune response to complex infectious disease such as tuberculosis, leading to improved experimental models and systems for improving our mechanistic understanding of why some individuals control the infection whereas others go on to develop active disease.
    MeSH term(s) Animals ; Biomarkers/metabolism ; Communicable Diseases/metabolism ; Disease Models, Animal ; Humans ; Infectious Disease Medicine ; Interferons/metabolism ; Lung/pathology ; Mice ; Mycobacterium tuberculosis/metabolism ; Systems Biology ; Transcription, Genetic ; Transcriptome ; Tuberculosis/immunology ; Tuberculosis/physiopathology
    Chemical Substances Biomarkers ; Interferons (9008-11-1)
    Language English
    Publishing date 2013-10-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1943-4456 ; 0091-7451
    ISSN (online) 1943-4456
    ISSN 0091-7451
    DOI 10.1101/sqb.2013.78.020172
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