Murine CTLA4-IgG Treatment Inhibits Airway Eosinophilia and Hyperresponsiveness and Attenuates IgE Upregulation in a Murine Model of Allergic Asthma

Oosterhout, Antoon J. M. van; Hofstra, Claudia L.; Shields, Robert L.; Chan, Betty; Ark, Ingrid van; Jardieu, Paula; Nijkamp, Frans P.

doi:10.1165/ajrcmb.17.3.2679

Cited by 86 publications

(64 citation statements)

References 27 publications

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“…After BAL and perfusion, lungs were excised, stored frozen at À801C and homogenized for 30 s in 1 mL of 0.05 M Tris/HCl buffer, pH 8.0. The homogenate was centrifuged for 15 min at 41C at 10 000 Â g. EPO activity in the supernatant was determined as estimated from the oxidation of O-phenylenediamine ( Sigma-Aldrich) by EPO in the presence of hydrogen peroxide using the protocol by Van Oosterhout et al [43]. The substrate solution consisted of 10 mM O-phenylenediamine in 0.05 M Tris/HCl-buffer (pH 5 8) and 4 mM H 2 O 2 (BDH, Poole, UK).…”

Section: Pulmonary Epo Activitymentioning

confidence: 99%

IL‐33‐activated dendritic cells are critical for allergic airway inflammation

et al. 2011

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IL-33, a new member of the IL-1 family cytokine, is involved in Th2-type responses in a wide range of diseases and signals through the ST2 receptor expressed on many immune cells. Since the effects of IL-33 on DCs remain controversial, we investigated the ability of IL-33 to modulate DC functions in vitro and in vivo. Here, we report that IL-33 activates myeloid DCs to produce IL-6, IL-1b, TNF, CCL17 and to express high levels of CD40, CD80 OX40L and CCR7. Importantly, IL-33-activated DCs prime naive lymphocytes to produce the Th2 cytokines IL-5 and IL-13, but not IL-4. In vivo, IL-33 exposure induces DC recruitment and activation in the lung. Using an OVA-induced allergic lung inflammation model, we demonstrate that the reduced airway inflammation in ST2-deficient mice correlates with the failure in DC activation and migration to the draining LN. Finally, we show that adoptive transfer of IL-33-activated DCs exacerbates lung inflammation in a DC-driven model of allergic airway inflammation. These data demonstrate for the first time that IL-33 activates DCs during antigen presentation and thereby drives a Th2-type response in allergic lung inflammation. IntroductionAllergic asthma is a chronic disorder characterized by eosinophilic airway inflammation, mucus hypersecretion, antigenspecific-IgE antibodies, airway remodeling and increased airway hyperreactivity [1,2]. The process of airway inflammation involves various cells types, such as eosinophils, mast cells, epithelial cells, lymphocytes and DCs. Th2 cells have been shown to play a predominant role in allergic asthma and Th2 cytokines, such as IL-4, IL-5 and IL-13, exacerbate disease severity [3,4]. IL-33, the recently discovered Th2 cytokine, is found at high levels in the plasma of asthmatic patients [5,6] and in the lungs of mice during experimental allergic asthma [7,8].IL-33 is a member of IL-1 family [9][10][11]. Like IL-1b or IL-18, IL-33 is synthesized as a precursor and can be cleaved by caspase-1 and 3 but the cleavage products are biologically less active than the precursor [12,13]. In contrast to the other IL-1 family members, IL-33 is mainly expressed in non-hematopoietic cells such as fibroblasts, epithelial cells and endothelial cells [10,14,15]. Because of its nuclear localization sequence, IL-33 is usually present in the nucleus, where it acts as a potential transcriptional repressor [16]. Recently, IL-33 has been shown to be released from necrotic cells and may act as an alarmin in a similar manner to IL-1a [17] or high mobility group box1 protein HMGB1 [18,19]. [14]. In accordance with its Th2 functions, administration of IL-33 into naive mice induces severe inflammation in the lung and digestive tract with elevated levels of IL-4, IL-5 and IL-13, splenomegaly and increased serum Ig [10]. In vitro, IL-33 has also been reported to polarize naive CD4 1 T cells to produce IL-5 and IL-13, but not . Polarization of this atypical Th2 population is independent of IL-4, STAT6 and GATA3. On macrophages, IL-33 amplifies IL-13-mediated polarization...

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Section: Pulmonary Epo Activitymentioning

confidence: 99%

IL‐33‐activated dendritic cells are critical for allergic airway inflammation

et al. 2011

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“…Peripheral blood eosinophilia and tumor-associated tissue eosinophilia are associated with objective responses during immunotherapy with interleukin-2, IL-4, granulocyte-macrophage colony-stimulating factor, and anti CTLA-4. 66,69 Treatment of tumor cells with irradiation or heat shock followed by membrane disruption was found to promote the release of IL-1a and the ICE-dependent recruitment of neutrophils towards dying tumor cells. In view of the fact that neutrophils could contribute to the elicitation of longterm antigen-specific CTL responses in melanoma models, 70 this result suggests that dying tumor cells can induce nonspecific inflammatory reaction that, in turn, may elicit a specific immune response.…”

Section: Cell Death and The Link Between Innate And Acquired Immunitymentioning

confidence: 99%

Tumor stress, cell death and the ensuing immune response

et al. 2007

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“…Although there is a significant amount of data suggesting that CD28 may preferentially affect the differentiation to T H 2 cells in vitro (12,13), as well as in vivo (11,14), this remains an unclarified point because there are reports of CD28-independent T H 2 responses in vitro (15) and in vivo (16). Whether CD28 signals affect the ability of T cells to develop into T H 2 cells or their subsequent secretion of cytokine is not clear; however, CD28 signals have been demonstrated to be required for the development of allergic asthma in mice (17)(18)(19)(20)(21). The CD28 related costimulatory molecule inducible costimulator molecule has also been demonstrated to be involved in regulating the pathology of either a Shistosoma mansoni model of allergic airway disease (22) or an OVA model of asthma in mice (23).…”

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confidence: 99%

Attenuation of Immunological Symptoms of Allergic Asthma in Mice Lacking the Tyrosine Kinase ITK

Mueller

August

2003

The Journal of Immunology

147

137

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Allergic asthma patients manifest airway inflammation and some show increases in eosinophils, TH2 cells, and cytokines, increased mucous production in the lung, and elevated serum IgE. This TH2-type response suggests a prominent role for TH2 cells and their cytokines in the pathology of this disease. The Tec family nonreceptor tyrosine kinase inducible T cell kinase (ITK) has been shown to play a role in the differentiation and/or function of TH2-type cells, suggesting that ITK may represent a good target for the control of asthma. Using a murine model of allergic asthma, we show here that ITK is involved in the development of immunological symptoms seen in this model. We show that mice lacking ITK have drastically reduced lung inflammation, eosinophil infiltration, and mucous production following induction of allergic asthma. Notably, T cell influx into the lung was reduced in mice lacking ITK. T cells from ITK−/− mice also exhibited reduced proliferation and cytokine secretion, in particular IL-5 and IL-13, in response to challenge with the allergen OVA, despite elevated levels of total IgE and increased OVA-specific IgE responses. Our results suggest that the tyrosine kinase ITK preferentially regulates the secretion of the TH2 cytokines IL-5 and IL-13 and may be an attractive target for antiasthmatic drugs.

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Murine CTLA4-IgG Treatment Inhibits Airway Eosinophilia and Hyperresponsiveness and Attenuates IgE Upregulation in a Murine Model of Allergic Asthma

Cited by 86 publications

References 27 publications

IL‐33‐activated dendritic cells are critical for allergic airway inflammation

IL‐33‐activated dendritic cells are critical for allergic airway inflammation

Tumor stress, cell death and the ensuing immune response

Attenuation of Immunological Symptoms of Allergic Asthma in Mice Lacking the Tyrosine Kinase ITK

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