scholarly journals Central role of immunoglobulin (Ig) E in the induction of lung eosinophil infiltration and T helper 2 cell cytokine production: inhibition by a non-anaphylactogenic anti-IgE antibody.

1996 ◽  
Vol 183 (4) ◽  
pp. 1303-1310 ◽  
Author(s):  
A J Coyle ◽  
K Wagner ◽  
C Bertrand ◽  
S Tsuyuki ◽  
J Bews ◽  
...  
Keyword(s):  
Cytokine Production ◽  
Serum Levels ◽  
Airway Disease ◽  
Cell Receptor ◽  
Allergic Airway Disease ◽  
Antigen Challenge ◽  
Eosinophil Infiltration ◽  
T Helper ◽  
Ige Antibody ◽  
Th2 Immune Response

Elevated levels of immunoglobulin (Ig) E are associated with bronchial asthma, a disease characterized by eosinophilic inflammation of the airways. Activation of antigen-specific T helper (Th) 2 cells in the lung with the subsequent release of interleukin (IL) 4 and IL-5 is believed to play an important role in the pathogenesis of this disease. In this study, we have used a non-anaphylactogenic anti-mouse-IgE antibody to investigate the relationship between IgE, airway eosinophil infiltration, and the production of Th2 cytokines. Immunization of mice with house dust mite antigen increased serum levels of IgE and IgG. Antigen challenge of immunized but not control mice induced an infiltration of eosinophils in the bronchoalveolar lavage associated with the production of IL-4 and IL-5 from lung purified Thy1.2+ cells activated through the CD3-T cell receptor complex. Administration of the anti-IgE monoclonal antibody (mAb) 6h before antigen challenge neutralized serum IgE but not IgG and inhibited the recruitment of eosinophils into the lungs and the production of IL-4 and IL-5 but not interferon gamma. Studies performed using an anti-CD23 mAb, CD23 deficient and mast cell deficient mice suggest that anti-IgE mAb suppresses eosinophil infiltration and Th2 cytokine production by inhibiting IgE-CD23-facilitated antigen presentation to T cells. Our results demonstrate that IgE-dependent mechanisms are important in the induction of a Th2 immune response and the subsequent infiltration of eosinophils into the airways. Neutralization of IgE, for example, non-anaphylactogenic anti-IgE mAbs may provide a novel therapeutic approach to the treatment of allergic airway disease.

scholarly journals Maternal endotoxin exposure attenuates allergic airway disease in infant rats

2010 ◽  
Vol 298 (5) ◽  
pp. L670-L677 ◽  
Author(s):  
Lei Cao ◽  
Jinxia Wang ◽  
Yingchun Zhu ◽  
Irene Tseu ◽  
Martin Post
Keyword(s):  
Transcription Factors ◽  
Cell Differentiation ◽  
T Cell ◽  
Airway Disease ◽  
Positive Control ◽  
Allergic Airway Disease ◽  
T Helper ◽  
T Helper 1 ◽  
Pregnant Rats ◽  
Neonatal Immune System

Prenatal exposures to immunogenic stimuli, such as bacterial LPS, have shown to influence the neonatal immune system and lung function. However, no detailed analysis of the immunomodulatory effects of LPS on postnatal T helper cell differentiation has been performed. Using a rat model, we investigated the effect of prenatal LPS exposure on postnatal T cell differentiation and experimental allergic airway disease. Pregnant rats were injected with LPS on day 20 and 21 (term = 22 days). Some of the offspring were sensitized and challenged with ovalbumin. Positive control animals were placebo exposed to saline instead of LPS, whereas negative controls were sensitized with saline. Expression of T cell-related transcription factors and cytokines was quantified in the lung, and airway hyperresponsiveness was measured. Prenatal LPS exposure induced a T helper 1 (TH1) immune milieu in the offspring of rats [i.e., increased T-bet and TH1 cytokine expression while expression of TH2-associated transcription factors (GATA3 and STAT6) and cytokines was decreased]. Prenatal LPS exposure did not trigger TH17 cell differentiation in the offspring. Furthermore, prenatal LPS exposure reduced ovalbumin-induced (TH2-mediated) airway inflammation, eosinophilia, and airway responsiveness. Thus, in utero exposure to endotoxin promotes a TH1 immune environment, which suppresses the development of allergic airway disease later in life.

scholarly journals Bacillus clausii, a Foreshore-Derived Probiotic, Attenuates Allergic Airway Inflammation Through Downregulation of Hypoxia Signaling

2020 ◽  
Vol 27 (2) ◽  
pp. 108-116
Author(s):  
Hyelim Park ◽  
Ah-Yeoun Jung ◽  
Chung-Soon Chang ◽  
Young Hyo Kim
Keyword(s):  
Pulmonary Inflammation ◽  
Allergic Airway Inflammation ◽  
Lung Parenchyma ◽  
Airway Disease ◽  
Lavage Fluid ◽  
Specific Ige ◽  
Allergic Airway Disease ◽  
Eosinophil Infiltration ◽  
Bacillus Clausii ◽  
Lung Histopathology

Background and Objectives: The immunomodulatory effects and mechanism of probiotics in allergic airway disease are largely unknown. We studied whether <i>Bacillus clausii</i> (BC), a probiotic derived from mudflats, had anti-allergic effects and compared the results with those of <i>Lactobacillus paracasei</i> (LP). We also examined whether the anti-allergic mechanisms of probiotics are associated with hypoxia signaling.Materials and Method: Forty-two BALB/c mice were randomly assigned to six experimental groups: controls, ovalbumin (OVA)-induced mice for inducing asthma, and OVA-induced mice that were orally administered LP or BC, at 1×10<sup>9</sup> or 5×10<sup>9</sup> CFU/mL each. We performed differential cell count testing on bronchoalveolar lavage fluid (BALF), lung histopathology, serum totals and OVA-specific IgE and IgG1 assessments, Th2 cytokine titers (IL-4, IL-5) in BALF and pulmonary parenchyma, quantitative PCR for <i>heme oxygenase (HO)-1</i> and <i>Hif-1α</i>, and immunohistochemistry.Results: Compared to the OVA group mice, OVA-sensitized mice treated with LP or BC showed significantly reduced numbers of eosinophils and neutrophils in the BALF (p<0.05). Both probiotics also significantly reduced pulmonary inflammation and eosinophil infiltration. Mice in the LP or BC group had a substantially lower titer of IL-4 and IL-5 in BALF, and decreased IL-4 and IL-5 expression in the lung parenchyma. Real-time PCR and immunohistochemistry showed that both LP and BC could significantly suppress <i>HO-1</i> and <i>Hif-1α</i> expression in asthmatic mice (p<0.05).Conclusion: BC can attenuate murine allergic asthma by regulating HIF-1α signaling, and its anti-allergic effect is comparable to that of LP.

scholarly journals Cc Chemokine Receptor (Ccr)3/Eotaxin Is Followed by Ccr4/Monocyte-Derived Chemokine in Mediating Pulmonary T Helper Lymphocyte Type 2 Recruitment after Serial Antigen Challenge in Vivo

2000 ◽  
Vol 191 (2) ◽  
pp. 265-274 ◽  
Author(s):  
Clare M. Lloyd ◽  
Tracy Delaney ◽  
Trang Nguyen ◽  
Jane Tian ◽  
Carlos Martinez-A ◽  
...  
Keyword(s):  
Chemokine Receptor ◽  
Progressive Increase ◽  
Allergic Airway Disease ◽  
Antigen Challenge ◽  
Th2 Cells ◽  
T Helper ◽  
Cc Chemokine

Isolated peripheral blood CD4 cells from allergic individuals express CC chemokine receptor (CCR)3 and CCR4 after expansion in vitro. In addition, human T helper type 2 (Th2) cells polarized in vitro selectively express CCR3 and CCR4 at certain stages of activation/differentiation and respond preferentially to the ligands eotaxin and monocyte-derived chemokine (MDC). However, controversy arises when the in vivo significance of this distinct expression is discussed. To address the functional role of CCR3/eotaxin and CCR4/MDC during the in vivo recruitment of Th2 cells, we have transferred effector Th cells into naive mice to induce allergic airway disease. Tracking of these cells after repeated antigen challenge has established that both CCR3/eotaxin and CCR4/MDC axes contribute to the recruitment of Th2 cells to the lung, demonstrating the in vivo relevance of the expression of these receptors on Th2 cells. We have shown that involvement of the CCR3/eotaxin pathway is confined to early stages of the response in vivo, whereas repeated antigen stimulation results in the predominant use of the CCR4/MDC pathway. We propose that effector Th2 cells respond to both CCR3/eotaxin and CCR4/MDC pathways initially, but that a progressive increase in CCR4-positive cells results in the predominance of the CCR4/MDC axis in the long-term recruitment of Th2 cells in vivo.

scholarly journals IL-18 Does not Increase Allergic Airway Disease in Mice When Produced by BCG

2007 ◽  
Vol 2007 ◽  
pp. 1-9
Author(s):  
L. Amniai ◽  
F. Biet ◽  
P. Marquillies ◽  
C. Locht ◽  
J. Pestel ◽  
...  
Keyword(s):  
Cytokine Production ◽  
Airway Disease ◽  
Mycobacterial Infection ◽  
Allergic Airway Disease ◽  
Murine Models ◽  
Mucus Production ◽  
Th2 Cytokine ◽  
Secondary Challenge ◽  
Th2 Responses ◽  
Airway Responses

Whilst BCG inhibits allergic airway responses in murine models, IL-18 has adversary effects depending on its environment. We therefore constructed a BCG strain producing murine IL-18 (BCG-IL-18) and evaluated its efficiency to prevent an asthma-like reaction in mice. BALB/cByJ mice were sensitized (day (D) 1 and D10) by intraperitoneal injection of ovalbumin (OVA)-alum and primary (D20–22) and secondary (D62, 63) challenged with OVA aerosols. BCG or BCG-IL-18 were intraperitonealy administered 1 hour before each immunization (D1 and D10). BCG-IL-18 and BCG were shown to similarly inhibit the development of AHR, mucus production, eosinophil influx, and local Th2 cytokine production in BAL, both after the primary and secondary challenge. These data show that IL-18 did not increase allergic airway responses in the context of the mycobacterial infection, and suggest that BCG-IL-18 and BCG are able to prevent the development of local Th2 responses and therefore inhibit allergen-induced airway responses even after restimulation.

scholarly journals Alterations of the Murine Gut Microbiome with Age and Allergic Airway Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Marius Vital ◽  
Jack R. Harkema ◽  
Mike Rizzo ◽  
James Tiedje ◽  
Christina Brandenberger
Keyword(s):  
Community Structure ◽  
Gut Microbiota ◽  
Serum Levels ◽  
The Elderly ◽  
Airway Disease ◽  
Allergic Airway Disease ◽  
Intestinal Microbiome ◽  
16S Rrna Analysis ◽  
Cytokine Analysis ◽  
Old Mice

The gut microbiota plays an important role in the development of asthma. With advanced age the microbiome and the immune system are changing and, currently, little is known about how these two factors contribute to the development of allergic asthma in the elderly. In this study we investigated the associations between the intestinal microbiome and allergic airway disease in young and old mice that were sensitized and challenged with house dust mite (HDM). After challenge, the animals were sacrificed, blood serum was collected for cytokine analysis, and the lungs were processed for histopathology. Fecal pellets were excised from the colon and subjected to 16S rRNA analysis. The microbial community structure changed with age and allergy development, where alterations in fecal communities from young to old mice resembled those after HDM challenge. Allergic mice had induced serum levels of IL-17A and old mice developed a greater allergic airway response compared to young mice. This study demonstrates that the intestinal bacterial community structure differs with age, possibly contributing to the exaggerated pulmonary inflammatory response in old mice. Furthermore, our results show that the composition of the gut microbiota changes with pulmonary allergy, indicating bidirectional gut-lung communications.

Oral administration of Lactobacillus salivarius inhibits the allergic airway response in mice

2010 ◽  
Vol 56 (5) ◽  
pp. 373-379 ◽  
Author(s):  
Chia-Yang Li ◽  
Hung-Chih Lin ◽  
Kai-Chung Hsueh ◽  
Shu-Fen Wu ◽  
Shih-Hua Fang
Keyword(s):  
Therapeutic Potential ◽  
Oral Treatment ◽  
Inflammatory Cells ◽  
Airway Disease ◽  
Specific Ige ◽  
Allergic Airway Disease ◽  
Antigen Challenge ◽  
Lactobacillus Salivarius ◽  
Airway Response ◽  
Antibody Levels

Asthma is recognized throughout the world as a chronic airway inflammatory disease. In this study, we investigated the effect of probiotics in response to antigen challenge in an ovalbumin (OVA)-sensitized asthma model in BALB/c mice. Lactobacillus salivarius PM-A0006 was orally administered to mice before antigen challenge. After antigen challenge, serum OVA-specific antibody levels, airway responsiveness to methacholine, influx of inflammatory cells to the lung, and cytokine levels in bronchoalveolar lavage (BAL) fluid and splenocytes were assessed. Oral treatment with live L. salivarius PM-A0006 significantly attenuated the influx of eosinophils to the airway lumen and reduced the levels of serum OVA-specific IgE and eotaxin in BAL fluid of antigen-challenged animals. Furthermore, L. salivarius PM-A0006 also decreased allergen-induced airway hyperresponsiveness and elevated the levels of IFN-γ. These results showed that oral treatment with L. salivarius PM-A0006 could have therapeutic potential in the treatment of allergic airway disease.

scholarly journals Activin-A induces regulatory T cells that suppress T helper cell immune responses and protect from allergic airway disease

2009 ◽  
Vol 206 (8) ◽  
pp. 1769-1785 ◽  
Author(s):  
Maria Semitekolou ◽  
Themis Alissafi ◽  
Maria Aggelakopoulou ◽  
Evangelia Kourepini ◽  
Harsha H. Kariyawasam ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Transforming Growth Factor ◽  
Allergen Challenge ◽  
Airway Disease ◽  
Activin A ◽  
Allergic Airway Disease ◽  
Cell Mediated Immunity ◽  
T Helper ◽  
Th2 Responses

Activin-A is a pleiotropic cytokine that participates in developmental, inflammatory, and tissue repair processes. Still, its effects on T helper (Th) cell–mediated immunity, critical for allergic and autoimmune diseases, are elusive. We provide evidence that endogenously produced activin-A suppresses antigen-specific Th2 responses and protects against airway hyperresponsiveness and allergic airway disease in mice. Importantly, we reveal that activin-A exerts suppressive function through induction of antigen-specific regulatory T cells that suppress Th2 responses in vitro and upon transfer in vivo. In fact, activin-A also suppresses Th1-driven responses, pointing to a broader immunoregulatory function. Blockade of interleukin 10 and transforming growth factor β1 reverses activin-A–induced suppression. Remarkably, transfer of activin-A–induced antigen-specific regulatory T cells confers protection against allergic airway disease. This beneficial effect is associated with dramatically decreased maturation of draining lymph node dendritic cells. Therapeutic administration of recombinant activin-A during pulmonary allergen challenge suppresses Th2 responses and protects from allergic disease. Finally, we demonstrate that immune cells infiltrating the lungs from individuals with active allergic asthma, and thus nonregulated inflammatory response, exhibit significantly decreased expression of activin-A's responsive elements. Our results uncover activin-A as a novel suppressive factor for Th immunity and a critical controller of allergic airway disease.

scholarly journals Costimulation through B7-2 (CD86) Is Required for the Induction of a Lung Mucosal T Helper Cell 2 (TH2) Immune Response and Altered Airway Responsiveness

1997 ◽  
Vol 185 (9) ◽  
pp. 1671-1680 ◽  
Author(s):  
Shogo Tsuyuki ◽  
Junko Tsuyuki ◽  
Karin Einsle ◽  
Manfred Kopf ◽  
Anthony J. Coyle
Keyword(s):  
Immune Response ◽  
Allergen Exposure ◽  
T Helper Cell ◽  
Helper Cell ◽  
Eosinophil Infiltration ◽  
T Helper ◽  
Th2 Cytokine ◽  
Th2 Immune Response ◽  
Eosinophil Accumulation

The recruitment of eosinophils into the airways after allergen exposure is dependent on interleukin (IL) 5 secreted from antigen-specific CD4+ T cells of the T helper cell (Th) 2 subset. However, while it is established that costimulation through CD28 is required for TCR-mediated activation and IL-2 production, the importance of this mechanism for the induction of a Th2 immune response is less clear. In the present study, we administered the fusion protein CTLA-4 immunoglobulin (Ig) into the lungs before allergen provocation to determine whether CD28/CTLA-4 ligands are required for allergen-induced eosinophil accumulation and the production of Th2 cytokines. Administration of CTLA-4 Ig inhibited the recruitment of eosinophils into the lungs by 75% and suppressed IgE in the bronchoalveolar lavage fluid. CTLA-4 Ig also inhibited the production of IL-4, IL-5, and IL-10 by 70–80% and enhanced interferon-γ production from CD3–T cell receptor–activated lung Thy1.2+ cells. Allergen exposure upregulated expression of B7-2, but not B7-1, on B cells from the lung within 24 h. Moreover, airway administration of an anti-B7-2 monoclonal antibody (mAb) inhibited eosinophil infiltration, IgE production, and Th2 cytokine secretion comparable in magnitude to that observed with CTLA-4 Ig. Treatment with an anti-B7-1 mAb had a small, but significant effect on eosinophil accumulation, although was less effective in inhibiting Th2 cytokine production. The anti-B7-2, but not anti-B7-1, mAb also inhibited antigen-induced airway hyperresponsiveness in vivo. In all of the parameters assessed, the combination of both the anti-B7-1 and anti-B7-2 mAb was no more effective than anti-B7-2 mAb treatment alone. We propose that strategies aimed at inhibition of CD28 interactions with B7-2 molecules may represent a novel therapeutic target for the treatment of lung mucosal allergic inflammation.

The CX3C-Chemokine Fractalkine (CX3CL1) is Detectable in Serum of Patients Affected by the Inflammatory Diseases Allergic Rhinitis and/or Asthma

2005 ◽  
Vol 3 (3) ◽  
pp. 149-152
Author(s):  
P.L. Minciullo ◽  
M. Patafi ◽  
L. Giannetto ◽  
R.A. Merendino ◽  
G. Di Pasquale ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Potential Role ◽  
Inflammatory Diseases ◽  
Allergic Diseases ◽  
Serum Levels ◽  
Airway Disease ◽  
High Serum ◽  
Allergic Airway Disease ◽  
Inflammatory Conditions ◽  
Healthy Donors

Fractalkine (FKN) is a chemokine able to mediate the initial capture, firm adhesion, and activation of circulating leukocytes. Many tissues express FKN mRNA and FKN expression is increased during inflammatory conditions. To assess a possible involvement in allergic airway disease, we detected serum levels of FKN in a group of patients affected by allergic rhinitis and/or asthma and found high serum levels of FKN in all patients and in only 26% of healthy donors at lower concentrations. The present results underscore the potential role that this chemokine may play in the pathogenesis of respiratory allergic diseases.

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