Eotaxin/CCL11 is involved in acute, but not chronic, allergic airway responses toAspergillus fumigatus

Eotaxin/CCL11 is a major chemoattractant for eosinophils and Th2 cells. As such, it represents an attractive target in the treatment of allergic disease. The present study addresses the role of eotaxin/CCL11 during acute and chronic allergic airway responses to the fungus Aspergillus fumigatus. Mice lacking the eotaxin gene (Eo−/−) and wild-type mice (Eo+/+) were sensitized to A. fumigatus and received either an intratracheal challenge with soluble A. fumigatusantigens (acute model) or an intratracheal challenge with live A. fumigatus spores or conidia (chronic model). Airway hyperresponsiveness and eosinophil, but not T cell, recruitment were significantly decreased at 24 h after the soluble allergen in A. fumigatus-sensitized Eo−/− mice compared with similarly sensitized Eo+/+ mice. In contrast, the development of chronic allergic airway disease due to A. fumigatus conidia was not altered by the lack of eotaxin. Together, these data suggest that eotaxin initiates allergic airway disease due to A. fumigatus, but this chemokine did not appear to contribute to the maintenance of A. fumigatus-induced allergic airway disease.

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Potential of Immunoglobulin A to Prevent Allergic Asthma

Clinical and Developmental Immunology ◽

10.1155/2013/542091 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 24

Author(s):

Anouk K. Gloudemans ◽

Bart N. Lambrecht ◽

Hermelijn H. Smits

Keyword(s):

Allergic Asthma ◽

Immunoglobulin A ◽

Bronchial Hyperresponsiveness ◽

Airway Disease ◽

Epidemiological Studies ◽

Allergic Airway Disease ◽

Secretory Iga ◽

Th2 Cells ◽

Lower Airway

Allergic asthma is characterized by bronchial hyperresponsiveness, a defective barrier function, and eosinophilic lower airway inflammation in response to allergens. The inflammation is dominated by Th2 cells and IgE molecules and supplemented with Th17 cells in severe asthma. In contrast, in healthy individuals, allergen-specific IgA and IgG4 molecules are found but no IgE, and their T cells fail to proliferate in response to allergens, probably because of the development of regulatory processes that actively suppress responses to allergens. The presence of allergen-specific secretory IgA has drawn little attention so far, although a few epidemiological studies point at a reverse association between IgA levels and the incidence of allergic airway disease. This review highlights the latest literature on the role of mucosal IgA in protection against allergic airway disease, the mechanisms described to induce secretory IgA, and the role of (mucosal) dendritic cells in this process. Finally, we discuss how this information can be used to translate into the development of new therapies for allergic diseases based on, or supplemented with, IgA boosting strategies.

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Dichotomous role of TGF-β controls inducible regulatory T-cell fate in allergic airway disease through Smad3 and TGF-β–activated kinase 1

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2019.09.032 ◽

2020 ◽

Vol 145 (3) ◽

pp. 933-946.e4

Author(s):

Anthony Joetham ◽

Michaela Schedel ◽

Fangkun Ning ◽

Meiqin Wang ◽

Katsuyuki Takeda ◽

...

Keyword(s):

T Cell ◽

Cell Fate ◽

Regulatory T Cell ◽

Airway Disease ◽

Allergic Airway Disease

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Faculty Opinions recommendation of Pro-inflammatory role of natural killer cells in the development of allergic airway disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718231191.793489895 ◽

2014 ◽

Author(s):

Jacques Zimmer

Keyword(s):

Natural Killer Cells ◽

Natural Killer ◽

Airway Disease ◽

Allergic Airway Disease ◽

Killer Cells

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Effect of thromboxane antagonists on ozone-induced airway responses in dogs

Journal of Applied Physiology ◽

10.1152/jappl.1990.69.3.880 ◽

1990 ◽

Vol 69 (3) ◽

pp. 880-884 ◽

Cited By ~ 4

Author(s):

G. L. Jones ◽

C. G. Lane ◽

P. M. O'Byrne

Keyword(s):

Airway Hyperresponsiveness ◽

The Other ◽

Receptor Antagonists ◽

Thromboxane Receptor ◽

Before And After ◽

The Mean ◽

Airway Responses ◽

Control Infusion

Airway hyperresponsiveness after inhaled ozone in dogs may occur as a result of thromboxane release in the airway. In this study, two thromboxane receptor antagonists, L-655,240 and L-670,596, were used in doses that inhibit the response to an inhaled thromboxane mimetic, U-46619, to determine further the role of thromboxane in ozone-induced airway hyperresponsiveness. Dogs were studied on 2 days separated by 1 wk. On each day, the dogs inhaled ozone (3 ppm) for 30 min. On one randomly assigned day, 10 dogs received an infusion of L-655,240 (5 mg.kg-1.h-1) and 5 dogs received an infusion of L-670,596 (1 mg.kg-1.h-1); on the other day dogs received a control infusion. Airway responses to doubling doses of acetylcholine were measured before and after inhalation of ozone and were expressed as the concentration of acetylcholine giving a rise in resistance of 5 cmH2O.l-1.s from baseline (acetylcholine provocation concentration). The development of airway hyperresponsiveness after ozone was not inhibited by the thromboxane antagonists. The mean log difference in the acetylcholine provocative concentration before and after ozone on the L-655,240 treatment day was 0.62 +/- 0.12 (SE) and on the control day was 0.71 +/- 0.12 (P = 0.48); on the L-670,596 treatment day the mean log difference was 0.68 +/- 0.15 (SE) and on the control day it was 0.75 +/- 0.19 (P = 0.45). These results do not support an important role for thromboxane in causing ozone-induced airway hyperresponsiveness.

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Maternal endotoxin exposure attenuates allergic airway disease in infant rats

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00399.2009 ◽

2010 ◽

Vol 298 (5) ◽

pp. L670-L677 ◽

Cited By ~ 18

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.

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Investigating the Role of Relaxin in the Regulation of Airway Fibrosis in Animal Models of Acute and Chronic Allergic Airway Disease

Annals of the New York Academy of Sciences ◽

10.1196/annals.1282.029 ◽

2005 ◽

Vol 1041 (1) ◽

pp. 194-196 ◽

Cited By ~ 4

Author(s):

ISHANEE MOOKERJEE ◽

MIMI L.K. TANG ◽

NATASHA SOLLY ◽

GEOFFREY W. TREGEAR ◽

CHRISHAN S. SAMUEL

Keyword(s):

Animal Models ◽

Airway Disease ◽

Allergic Airway Disease ◽

Airway Fibrosis

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Systems Modeling of the Role of Interleukin-21 in the Maintenance of Effector CD4+ T Cell Responses during Chronic Helicobacter pylori Infection

mBio ◽

10.1128/mbio.01243-14 ◽

2014 ◽

Vol 5 (4) ◽

Cited By ~ 36

Author(s):

Adria Carbo ◽

Danyvid Olivares-Villagómez ◽

Raquel Hontecillas ◽

Josep Bassaganya-Riera ◽

Rupesh Chaturvedi ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

T Cell ◽

Wild Type ◽

Content Type ◽

Interleukin 21 ◽

H Pylori ◽

Deficient Mice

ABSTRACTThe development of gastritis duringHelicobacter pyloriinfection is dependent on an activated adaptive immune response orchestrated by T helper (Th) cells. However, the relative contributions of the Th1 and Th17 subsets to gastritis and control of infection are still under investigation. To investigate the role of interleukin-21 (IL-21) in the gastric mucosa duringH. pyloriinfection, we combined mathematical modeling of CD4+T cell differentiation within vivomechanistic studies. We infected IL-21-deficient and wild-type mice withH. pyloristrain SS1 and assessed colonization, gastric inflammation, cellular infiltration, and cytokine profiles. ChronicallyH. pylori-infected IL-21-deficient mice had higherH. pyloricolonization, significantly less gastritis, and reduced expression of proinflammatory cytokines and chemokines compared to these parameters in infected wild-type littermates. Thesein vivodata were used to calibrate anH. pyloriinfection-dependent, CD4+T cell-specific computational model, which then described the mechanism by which IL-21 activates the production of interferon gamma (IFN-γ) and IL-17 during chronicH. pyloriinfection. The model predicted activated expression of T-bet and RORγt and the phosphorylation of STAT3 and STAT1 and suggested a potential role of IL-21 in the modulation of IL-10. Driven by our modeling-derived predictions, we found reduced levels of CD4+splenocyte-specifictbx21androrcexpression, reduced phosphorylation of STAT1 and STAT3, and an increase in CD4+T cell-specific IL-10 expression inH. pylori-infected IL-21-deficient mice. Our results indicate that IL-21 regulates Th1 and Th17 effector responses during chronicH. pyloriinfection in a STAT1- and STAT3-dependent manner, therefore playing a major role controllingH. pyloriinfection and gastritis.IMPORTANCEHelicobacter pyloriis the dominant member of the gastric microbiota in more than 50% of the world’s population.H. pyloricolonization has been implicated in gastritis and gastric cancer, as infection withH. pyloriis the single most common risk factor for gastric cancer. Current data suggest that, in addition to bacterial virulence factors, the magnitude and types of immune responses influence the outcome of colonization and chronic infection. This study uses a combined computational and experimental approach to investigate how IL-21, a proinflammatory T cell-derived cytokine, maintains the chronic proinflammatory T cell immune response driving chronic gastritis duringH. pyloriinfection. This research will also provide insight into a myriad of other infectious and immune disorders in which IL-21 is increasingly recognized to play a central role. The use of IL-21-related therapies may provide treatment options for individuals chronically colonized withH. pylorias an alternative to aggressive antibiotics.

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CCSP modulates airway dysfunction and host responses in an Ova-challenged mouse model

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.2001.281.5.l1303 ◽

2001 ◽

Vol 281 (5) ◽

pp. L1303-L1311 ◽

Cited By ~ 38

Author(s):

Shan-Ze Wang ◽

Cynthia L. Rosenberger ◽

Teresa M. Espindola ◽

Edward G. Barrett ◽

Yohannes Tesfaigzi ◽

...

Keyword(s):

Airway Epithelium ◽

Host Response ◽

Secretory Protein ◽

Allergic Airway Disease ◽

Clara Cell ◽

Myeloperoxidase Activity ◽

Wild Type ◽

Airway Reactivity ◽

Mucus Production

Clara cell secretory protein (CCSP) is synthesized by nonciliated bronchiolar cells in the lung and modulates lung inflammation to infection. To determine the role of CCSP in the host response to allergic airway disease, CCSP-deficient [(−/−)] mice were immunized twice with ovalbumin (Ova) and challenged by Ova (2 or 5 mg/m3) aerosol. After 2, 3, and 5 days of Ova aerosol challenge (6 h/day), airway reactivity was increased in CCSP(−/−) mice compared with wild-type [CCSP(+/+)] mice. Neutrophils were markedly increased in the bronchoalveolar lavage fluid of CCSP(−/−) Ova mice, coinciding with increased myeloperoxidase activity and macrophage inflammatory protein-2 levels. Lung histopathology and inflammation were increased in CCSP(−/−) compared with wild-type mice after Ova challenge. Mucus production, as assessed by histological staining, was increased in the airway epithelium of CCSP(−/−) Ova mice compared with that in CCSP(+/+) Ova mice. These data suggest a role for CCSP in airway reactivity and the host response to allergic airway inflammation and provide further evidence for the role of the airway epithelium in regulating airway responses in allergic disease.

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Role of TNFR1 in the innate airway hyperresponsiveness of obese mice

Journal of Applied Physiology ◽

10.1152/japplphysiol.00588.2012 ◽

2012 ◽

Vol 113 (9) ◽

pp. 1476-1485 ◽

Cited By ~ 11

Author(s):

Ming Zhu ◽

Alison S. Williams ◽

Lucas Chen ◽

Allison P. Wurmbrand ◽

Erin S. Williams ◽

...

Keyword(s):

Airway Hyperresponsiveness ◽

Bronchoalveolar Lavage Fluid ◽

Pulmonary Inflammation ◽

Tumor Necrosis Factor Receptor ◽

Lavage Fluid ◽

Forced Oscillation Technique ◽

Obese Mice ◽

Wild Type ◽

Necrosis Factor

The purpose of this study was to examine the role of tumor necrosis factor receptor 1 (TNFR1) in the airway hyperresponsiveness characteristic of obese mice. Airway responsiveness to intravenous methacholine was measured using the forced oscillation technique in obese Cpe fat mice that were either sufficient or genetically deficient in TNFR1 ( Cpe fat and Cpe fat/TNFR1−/− mice) and in lean mice that were either sufficient or genetically deficient in TNFR1 [wild-type (WT) and TNFR1−/− mice]. Compared with lean WT mice, Cpe fat mice exhibited airway hyperresponsiveness. Airway hyperresponsives was also greater in Cpe fat/TNFR1−/− than in Cpe fat mice. Compared with WT mice, Cpe fat mice had increases in bronchoalveolar lavage fluid concentrations of several inflammatory moieties including eotaxin, IL-9, IP-10, KC, MIG, and VEGF. These factors were also significantly elevated in Cpe fat/TNFR1−/− vs. TNFR1−/− mice. Additional moieties including IL-13 were also elevated in Cpe fat/TNFR1−/− vs. TNFR1−/− mice but not in Cpe fat vs. WT mice. IL-17A mRNA expression was greater in Cpe fat/TNFR1−/− vs. Cpe fat mice and in TNFR1−/− vs. WT mice. Analysis of serum indicated that obesity resulted in systemic as well as pulmonary inflammation, but TNFR1 deficiency had little effect on this systemic inflammation. Our results indicate that TNFR1 is protective against the airway hyperresponsiveness associated with obesity and suggest that effects on pulmonary inflammation may be contributing to this protection.

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