IL-33 exacerbates eosinophil-mediated airway inflammation Stolarski, Bartosz; Kurowska-Stolarska, Mariola; Kewin, Peter ...
The Journal of immunology (1950),
2010-Sep-15, 2010-09-15, 20100915, Letnik:
185, Številka:
6
Journal Article
Recenzirano
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IL-33 has emerged as an important mediator in the immunopathogenesis of allergy and asthma. However, the role of IL-33 in eosinophil-mediated inflammation has not been fully explored. In this ...article, we report that IL-33 directly stimulates eosinophil differentiation from CD117(+) progenitors in an IL-5-dependent manner. Although resting eosinophils expressed moderate levels of the IL-33R alpha-chain (ST2L), eosinophils that accumulated in the airways of mice with OVA-induced asthma expressed increased amounts of ST2L. In vitro, IL-33 and GM-CSF are potent inducers of ST2L expression on eosinophils, and IL-33 induced the production of IL-13, CCL17, and TGF-beta by eosinophils. In adoptive-transfer experiments, IL-33 exacerbated eosinophil-mediated airway inflammation by increasing the levels of eosinophils, macrophages, lymphocytes, IL-13, TGF-beta, CCL3, CCL17, and CCL24 in the lungs. IL-33 also enhanced the eosinophil-mediated differentiation of airway macrophages toward the alternatively activated macrophage phenotype in an IL-13-dependent manner. Taken together, this study demonstrates that the IL-33/ST2 signaling pathway activates airway eosinophils that exacerbate airway inflammation in an autocrine and paracrine manner.
IL-33, a cytokine of the IL-1 family, is closely associated with type II T cell responses. Here, we report an unexpected proinflammatory role of IL-33 in inflammatory arthritis. IL-33 was expressed ...in synovial fibroblasts from patients with rheumatoid arthritis (RA). Expression was markedly elevated in vitro by inflammatory cytokines. Mice lacking ST2, the IL-33 receptor α-chain, developed attenuated collagen-induced arthritis (CIA) and reduced ex vivo collagen-specific induction of proinflammatory cytokines (IL-17, TNFα, and IFNγ), and antibody production. Conversely, treatment of wild-type (WT) but not ST2⁻/⁻ mice with IL-33 exacerbated CIA and elevated production of both proinflammatory cytokines and anti-collagen antibodies. Mast cells expressed high levels of ST2 and responded directly to IL-33 to produce a spectrum of inflammatory cytokines and chemokines in vitro. In vivo, IL-33 treatment exacerbated CIA in ST2⁻/⁻ mice engrafted with mast cells from WT but not from ST2⁻/⁻ mice. Disease exacerbation was accompanied by elevated expression levels of proinflammatory cytokines. Our results demonstrate that IL-33 is a critical proinflammatory cytokine for inflammatory joint disease that integrates fibroblast activation with downstream immune activation mainly via an IL-33-driven, mast-cell-dependent pathway. Thus, this IL-1 superfamily member represents a therapeutic target for RA.
Alternatively activated macrophages (AAM) play a crucial role in type 2 immunity. Mice deficient in ST2, a receptor for the latest member of the IL-1 family, IL-33, have impaired type 2 immune ...responses. We therefore reasoned that IL-33/ST2 signaling may be involved in the differentiation and activation of AAM during airway inflammation. We report here that IL-33 changed the quiescent phenotype of alveolar macrophages toward an AAM phenotype that expressed mannose receptor, IL-4Ralpha, and produced high levels of CCL24 and CCL17 in an IL-13-dependent manner during IL-33-induced airway inflammation. Neutralization of AAM-derived CCL24 led to an amelioration of IL-33-induced eosinophilia in the lungs. Moreover, depletion of alveolar macrophages reduced IL-33-induced airway inflammation. Additionally, the attenuated OVA-induced airway inflammation in ST2(-/-) mice was associated with a decrease in AAM differentiation. In vitro, IL-33 amplified IL-13-induced polarization of alveolar- and bone marrow-derived macrophage toward an AAM phenotype by increasing the expression of arginase I, Ym1, as well as the production of CCL24 and CCL17. IL-13/IL-4Ralpha signaling was crucial for IL-33-driven AAM amplification by inducing the expression of ST2L. Finally, we showed that IL-33 was more abundantly expressed in the lung epithelial cells of asthma patients than those from healthy controls, suggesting that IL-33 may be involved in lung macrophage activation in clinical asthma. Taken together, we demonstrate here that IL-33/ST2 plays a significant role in the amplification of AAM polarization and chemokine production which contribute to innate and Ag-induced airway inflammation.
We describe a patient with COVID-19 who developed simultaneous pulmonary, intracardiac and peripheral arterial thrombosis. A 58-year-old man, without major comorbidity, was admitted with a 14-day ...history of breathlessness. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection was confirmed by laboratory testing. Initial imaging revealed COVID-19 pneumonia but no pulmonary thromboembolism (PTE) on CT pulmonary angiography (CTPA). The patient subsequently developed respiratory failure and left foot ischaemia associated with a rising D-dimer. Repeat CTPA and lower limb CT angiography revealed simultaneous bilateral PTE, biventricular cardiac thrombi and bilateral lower limb arterial occlusions. This case highlights a broad range of vascular sequalae associated with COVID-19 and the fact that these can occur despite a combination of prophylactic and treatment dose anticoagulation.
We describe a patient with COVID-19 who developed simultaneous pulmonary, intracardiac and peripheral arterial thrombosis. A 58-year-old man, without major comorbidity, was admitted with a 14-day ...history of breathlessness. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection was confirmed by laboratory testing. Initial imaging revealed COVID-19 pneumonia but no pulmonary thromboembolism (PTE) on CT pulmonary angiography (CTPA). The patient subsequently developed respiratory failure and left foot ischaemia associated with a rising D-dimer. Repeat CTPA and lower limb CT angiography revealed simultaneous bilateral PTE, biventricular cardiac thrombi and bilateral lower limb arterial occlusions. This case highlights a broad range of vascular sequalae associated with COVID-19 and the fact that these can occur despite a combination of prophylactic and treatment dose anticoagulation.
The mechanism responsible for the induction of immunological tolerance by oral administration of soluble antigen remains unclear. Here we show that, when cultured in vitro in the absence of antigen, ...lymphocytes from mice tolerized with a single feed of 25 mg of ovalbumin display an enhanced mortality in comparison with cells from immunized control animals. This increased cell death affects both CD4+ and CD8+ T-lymphocyte subsets, and morphological and flow cytometric analyses suggest that it occurs via apoptosis. All of the changes associated with the propensity of tolerant cells to die by apoptosis in vitro are reduced by the inclusion of the tolerizing antigen in the cultures. These results suggest that tolerance to dietary proteins is accompanied by functional changes in T lymphocytes that render them susceptible to apoptosis. This mechanism may underlie the profound and permanent tolerance to food antigens found under physiological conditions and may provide a useful basis for immunotherapy.
This thesis reads British Boom science fiction and critical posthumanism as a proliferation of story engines, which are sites of ideation where the boundaries between disciplinary sites of ...meaning-making and world-forming are reconfigured and unsettled. Five exemplary writers of the post-1990s British Boom science fiction period – Matthew De Abaitua, Alastair Reynolds, Jeff Noon, Adam Roberts, and Justina Robson – explore different conceptualizations of the human in the time of the posthuman. For this, the emergence of a posthuman curator is necessary to account for both fiction and theory as entangled agencies, which unsettle normative assumptions about humanity, as the universal measure of things and as dominant species in the time of the Anthropocene. The conceptual argument is simple in its outline: the curator is a performative account of science fiction’s posthumanizing potential, where the curator occupies a diffractive framework (following Karen Barad) unsettling works of science fiction from the sanctity of categorisation and practices that limit its ability to explore that which cannot yet be imagined. The materiality of these texts and the phenomena which they enact – for all matter is enfolded with/in these story engines of British Boom science fiction – explore how the nature of change is changed through these entangled agential forces. These curators unsettle the status of individuals, human or otherwise, machines, animals, and species. This thesis therefore foregrounds the potential of science fiction as the encounter and transformation of humanity into something otherwise than human – the process which Stefan Herbrechter refers to as “posthumanization”.1 As such, other models of life – virtual, technological, animal – inform the tropes, the narrative arcs, and the subject positions possible in posthumanizing narratives.
A 28-year-old man treated with the antitumour necrosis factor α (TNFα) monoclonal antibody infliximab for Crohn's disease developed pulmonary tuberculosis (TB), despite testing negative for latent TB ...prior to treatment. On starting anti-TB treatment and withdrawal of the anti-TNFα therapy, he deteriorated both clinically and radiologically. He was diagnosed with a flare of Crohn's disease, and immune reconstitution inflammatory syndrome (IRIS) in his right upper lobe and mediastinal lymph nodes, and commenced on oral prednisolone. Anti-TNFα therapy was re-introduced, and prednisolone weaned, following 4 months of anti-TB treatment without complication. He made a full recovery from TB, although his Crohn's symptoms continue to be troublesome. There has been no reactivation of TB to date, after 2 years follow-up.
A 28-year-old man treated with the antitumour necrosis factor α (TNFα) monoclonal antibody infliximab for Crohn's disease developed pulmonary tuberculosis (TB), despite testing negative for latent TB ...prior to treatment. On starting anti-TB treatment and withdrawal of the anti-TNFα therapy, he deteriorated both clinically and radiologically. He was diagnosed with a flare of Crohn's disease, and immune reconstitution inflammatory syndrome (IRIS) in his right upper lobe and mediastinal lymph nodes, and commenced on oral prednisolone. Anti-TNFα therapy was re-introduced, and prednisolone weaned, following 4 months of anti-TB treatment without complication. He made a full recovery from TB, although his Crohn's symptoms continue to be troublesome. There has been no reactivation of TB to date, after 2 years follow-up.
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