Regulatory T cells and IL-10 in allergic inflammation

Recent studies suggest that human regulatory T (T reg) cells protect against the development of allergic and asthmatic disease and that their function is impaired during active disease. Two new studies contribute to our understanding of the role that T reg cells play in the control of allergic airway disease in mice. However, these studies also highlight several outstanding questions in the field

Regulatory T Cells in Asthma

Asthma is characterized by T helper cell 2 (Th2) type inflammation, leading to airway hyperresponsiveness and tissue remodeling. Th2 cell-driven inflammation is likely to represent an abnormal response to harmless airborne particles. These reactions are normally suppressed by regulatory T cells, which maintain airway tolerance. The anti-inflammatory cytokine IL-10 is likely to play a central role. The role of the cytokine transforming growth factor β (TGF-β) is more complex, with evidence for immune suppression and remodeling in the airways. In asthmatic individuals there is a breakdown in these regulatory mechanisms. There is emerging evidence that early life events, including exposure to allergen and infections, are critical in programming effective regulatory pathways to maintain pulmonary homeostasis. In this review we examine the clinical and experimental evidence for T regulatory cell function in the lung and discuss the events that might influence the functioning of these cells. Ultimately, the ability to enhance regulatory function in affected individuals may represent an effective treatment for asthma

Immunological intervention in human diseases

A recent Keystone Symposium Meeting on "Immunological Intervention in Human Disease" was held in Big Sky, Montana on January, 6–11, 2007, organized by Jacques Banchereau, Federica Sallusto and Robert Coffman. It brought together basic scientists and clinicians from both academia and the pharmaceutical industry to discuss how the immune system is involved in the development of human diseases, including cancer, allergy, autoimmunity, and infectious diseases. We highlight advances in our understanding of the pathogenesis of immune-mediated diseases and future approaches in the immune therapeutic interventions. Considerable progress in the development of model systems and methodologies to monitor human immune responses will help to develop and to evaluate new immune-based therapies at pre-clinical and clinical studies

Urban particulate matter stimulation of human dendritic cells enhances priming of naive CD8 T lymphocytes

Wellcome Trust. Grant Number: 098882/Z/12/Z National Institute for Health Research (NIHR

High-Dose IL-2 Skews a Glucocorticoid-Driven IL-17(+)IL-10(+) Memory CD4(+) T Cell Response towards a Single IL-10-Producing Phenotype

This is the accepted, uncopyedited version of the manuscript. The definitive version was published in J Immunol December 31, 2018, ji1800697; DOI: https://doi.org/10.4049/jimmunol.1800697This work was supported by the Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, which funded E.H.M., who initiated this work as a Ph.D. student. The research also received support from the National Institute for Health Research Biomedical Research Centre based at Guy’s and St Thomas’ National Health Service Foundation Trust and King’s College London. This work, as well as A.O., L.G., and E.H.M., was subsequently supported by the Francis Crick Institute (FC001126), which receives its core funding from Cancer Research UK, the UK Medical Research Council, and the Wellcome Trust

Exogenous sex steroid hormones and asthma in females:protocol for a population-based retrospective cohort study using a UK primary care database

This work was supported by Asthma UK, grant number: AUK-IG-2016-346. BIN, INS, CRS and AS were in addition support by the Farr Institute and Asthma UK Centre for Applied Research. BIN acknowledges the support of Knut and Alice Wallenberg Foundation and the Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Sweden.Peer reviewedPublisher PD

Biphasic activation of complement and fibrinolysis during the human nasal allergic response

Complement, coagulation and fibrinolysis contribute to the pathology of many respiratory diseases. Here we detail the biphasic activation of these pathways following nasal allergen challenge. Understanding these mechanisms may lead to therapeutic insight in common respiratory diseases

In Vitro Generation of Interleukin 10–producing Regulatory CD4+ T Cells Is Induced by Immunosuppressive Drugs and Inhibited by T Helper Type 1 (Th1)– and Th2-inducing Cytokines

We show that a combination of the immunosuppressive drugs, vitamin D3 and Dexamethasone, induced human and mouse naive CD4+ T cells to differentiate in vitro into regulatory T cells. In contrast to the previously described in vitro derived CD4+ T cells, these cells produced only interleukin (IL)-10, but no IL-5 and interferon (IFN)-γ, and furthermore retained strong proliferative capacity. The development of these IL-10–producing cells was enhanced by neutralization of the T helper type 1 (Th1)- and Th2–inducing cytokines IL-4, IL-12, and IFN-γ. These immunosuppressive drugs also induced the development of IL-10–producing T cells in the absence of antigen-presenting cells, with IL-10 acting as a positive autocrine factor for these T cells. Furthermore, nuclear factor (NF)-κB and activator protein (AP)-1 activities were inhibited in the IL-10–producing cells described here as well as key transcription factors involved in Th1 and Th2 subset differentiation. The regulatory function of these in vitro generated IL-10–producing T cells was demonstrated by their ability to prevent central nervous system inflammation, when targeted to the site of inflammation, and this function was shown to be IL-10 dependent. Generating homogeneous populations of IL-10–producing T cells in vitro will thus facilitate the use of regulatory T cells in immunotherapy

Hormone Replacement Therapy and Risk of Severe Asthma Exacerbation in Perimenopausal and Postmenopausal Women : 17-Year National Cohort Study

This work was supported by Asthma UK, grant number: AUK-IG-2016-346 and Health Data Research UK. We thank Optimum Patient Care (OPC) and Observational and Pragmatic Research Institute Pte Ltd (OPRI) for making the OPCRD database (www.opcrd.co.uk) available free of charge. B. I. Nwaru acknowledges the support of Knut and Alice Wallenberg Foundation, the Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Sweden, and the VBG Group Herman Krefting Foundation on Asthma and Allergy. A. Sheikh acknowledges support of Health Data Research UK (BREATHE).Peer reviewedPublisher PD