scholarly journals Matricellular Protein Periostin Promotes Pericyte Migration in Fibrotic Airways

2021 ◽  
Vol 2 ◽  
Author(s):  
Rebecca E. Bignold ◽  
Jill R. Johnson
Keyword(s):  
Allergic Asthma ◽  
Airway Remodeling ◽  
Airway Disease ◽  
Lavage Fluid ◽  
Allergic Airway Disease ◽  
Matricellular Protein ◽  
Large Airways ◽  
Migration Assays ◽  
Fibrotic Lung Disease

Introduction: Periostin is a matricellular protein that is currently used as a biomarker for asthma. However, its contribution to tissue remodeling in allergic asthma is currently unknown. We have previously demonstrated that tissue-resident mesenchymal stem cells known as pericytes are a key cell type involved in airway remodeling. This is thought to be caused the uncoupling of pericytes from the microvasculature supporting the large airways, facilitated by inflammatory growth factors and cytokines. It is hypothesized that periostin may be produced by profibrotic pericytes and contribute to the remodeling observed in allergic asthma.Methods: Lung sections from mice with allergic airway disease driven by exposure to house dust mite (HDM) were stained using an anti-periostin antibody to explore its involvement in fibrotic lung disease. Human pericytes were cultured in vitro and stained for periostin to assess periostin expression. Migration assays were performed using human pericytes that were pretreated with TGF-β or periostin. ELISAs were also carried out to assess periostin expression levels in bronchoalveolar lavage fluid as well as the induction of periostin production by IL-13.Results: Immunostaining indicated that pericytes robustly express periostin, with increased expression following treatment with TGF-β. Migration assays demonstrated that pericytes treated with periostin were more migratory. Periostin production was also increased in HDM exposed mice as well as in cultured pericytes treated with IL-13.Conclusion: Periostin is produced by pericytes in response to TGF-β or IL-13, and periostin plays a key role in inducing pericyte migration. The increase in periostin expression in TGF-β or IL-13 treated pericytes suggests that IL-13 may trigger periostin production in pericytes whilst TGF-β modulates periostin expression to promote pericyte migration in the context of tissue fibrosis.

scholarly journals Potential of Immunoglobulin A to Prevent Allergic Asthma

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
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.

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 Distinct functions of tissue-resident and circulating memory Th2 cells in allergic airway disease

2020 ◽  
Author(s):  
Rod A. Rahimi ◽  
Keshav Nepal ◽  
Murat Cetinbas ◽  
Ruslan I. Sadreyev ◽  
Andrew D. Luster
Keyword(s):  
Allergic Asthma ◽  
Allergic Airway Inflammation ◽  
Lung Parenchyma ◽  
Airway Disease ◽  
Gene Signature ◽  
Allergic Airway Disease ◽  
Transcriptional Analysis ◽  
Th2 Cells ◽  
Redundant Functions

ABSTRACTMemory CD4+ T helper type 2 (Th2) cells are critical in driving allergic asthma pathogenesis, yet the mechanisms whereby tissue-resident memory Th2 cells (Th2 Trm) and circulating memory Th2 cells collaborate in vivo remain unclear. Here, using a house dust mite (HDM) model of allergic asthma and parabiosis, we demonstrate that Th2 Trm and circulating memory Th2 cells perform non-redundant functions in vivo. Upon HDM re-challenge, circulating memory Th2 cells trafficked into the lung parenchyma and ignited perivascular inflammation to promote eosinophil and CD4+ T cell recruitment. In contrast, Th2 Trm proliferated near airways and promoted mucus metaplasia, airway hyper-responsiveness, and airway eosinophil activation. Transcriptional analysis revealed that Th2 Trm and circulating memory Th2 cells share a core Th2 gene signature, but also exhibit distinct transcriptional profiles. Specifically, Th2 Trm express a tissue adaptation signature, including genes involved in regulating and interacting with extracellular matrix. Our findings demonstrate that Th2 Trm and circulating memory Th2 cells are functionally and transcriptionally distinct subsets with unique roles in promoting allergic airway disease.SUMMARYHow memory Th2 cell subsets orchestrate allergic airway inflammation remains unclear. Rahimi et al. use a murine model of allergic asthma and parabiosis to demonstrate that tissue-resident and circulating memory Th2 cells are functionally distinct subsets with unique roles in promoting allergic airway disease.

Preclinical Safety and Pharmacology of an Anti-Human Interleukin-13 Monoclonal Antibody in Normal Macaques and in Macaques with Allergic Asthma

2008 ◽  
Vol 27 (5) ◽  
pp. 351-358 ◽  
Author(s):  
Pauline L. Martin ◽  
Dusti Fisher ◽  
William Glass ◽  
Karyn O’Neil ◽  
Anuk Das ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Allergic Asthma ◽  
Immunoglobulin E ◽  
Cynomolgus Macaque ◽  
Lavage Fluid ◽  
Antigen Challenge ◽  
Interleukin 13 ◽  
Lung Eosinophilia

Interleukin-13 (IL-13) plays a central role in chronic airway diseases, including asthma. These studies were conducted to evaluate the safety of administration of a human anti-IL-13 monoclonal antibody (mAb) to normal macaques and in macaques with allergic asthma. In addition, serum and bronchioalveolar lavage fluid were collected from allergic cynomolgus macaques in order to identify potential surrogate markers of IL-13 pharmacology that could be useful for subsequent clinical trials. In vitro studies demonstrated that the anti-IL-13 mAb inhibited the pharmacological actions of both human and cynomolgus macaque IL-13. Allergic macaques were treated systemically with 10 mg/kg anti-IL-13 mAb 1 day prior to inhaled Ascaris suum antigen challenge. Normal macaques were dosed intravenously with anti-IL-13 once per week for 3 weeks at doses of 10 or 50 mg/kg. Treatment of macaques with the anti-IL-13 mAb was not associated with any toxicologically significant findings. A slight treatment-related but nonadverse decrease in platelet counts was observed in both the normal and allergic macaques. In allergic macaques, the anti-IL-13 mAb treatment did not affect lung function, lung eosinophilia, or serum or BAL immunoglobulin E (IgE) concentrations but did produce a reduction in BAL and serum eotaxin concentrations ( p < .05) at 6 h post antigen challenge. This study shows that administration of an anti-IL-13 mAb was well tolerated in both normal and allergic asthmatic macaques and that serum eotaxin concentrations may be a useful early in vivo marker for evaluating IL-13 inhibition in patients with asthma.

Divergent immune responses to house dust mite lead to distinct structural-functional phenotypes

2007 ◽  
Vol 293 (3) ◽  
pp. L730-L739 ◽  
Author(s):  
Jill R. Johnson ◽  
Filip K. Swirski ◽  
Beata U. Gajewska ◽  
Ryan E. Wiley ◽  
Ramzi Fattouh ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Inflammatory Responses ◽  
Airway Remodeling ◽  
Bronchial Hyperresponsiveness ◽  
Airway Disease ◽  
Allergic Airway Disease ◽  
Th Cell ◽  
And Function ◽  
Deficient Mice ◽  
Chronic Airway

Asthma is a chronic airway inflammatory disease that encompasses three cardinal processes: T helper (Th) cell type 2 (Th2)-polarized inflammation, bronchial hyperreactivity, and airway wall remodeling. However, the link between the immune-inflammatory phenotype and the structural-functional phenotype remains to be fully defined. The objective of these studies was to evaluate the relationship between the immunologic nature of chronic airway inflammation and the development of abnormal airway structure and function in a mouse model of chronic asthma. Using IL-4-competent and IL-4-deficient mice, we created divergent immune-inflammatory responses to chronic aeroallergen challenge. Immune-inflammatory, structural, and physiological parameters of chronic allergic airway disease were evaluated in both strains of mice. Although both strains developed airway inflammation, the profiles of the immune-inflammatory responses were markedly different: IL-4-competent mice elicited a Th2-polarized response and IL-4-deficient mice developed a Th1-polarized response. Importantly, this chronic Th1-polarized immune response was not associated with airway remodeling or bronchial hyperresponsiveness. Transient reconstitution of IL-4 in IL-4-deficient mice via an airway gene transfer approach led to partial Th2 repolarization and increased bronchial hyperresponsiveness, along with full reconstitution of airway remodeling. These data show that distinct structural-functional phenotypes associated with chronic airway inflammation are strictly dependent on the nature of the immune-inflammatory response.

scholarly journals Airway Remodeling Is Absent in CCR1−/− Mice During Chronic Fungal Allergic Airway Disease

2000 ◽  
Vol 165 (3) ◽  
pp. 1564-1572 ◽  
Author(s):  
Kate Blease ◽  
Borna Mehrad ◽  
Theodore J. Standiford ◽  
Nicholas W. Lukacs ◽  
Steven L. Kunkel ◽  
...  
Keyword(s):  
Airway Remodeling ◽  
Airway Disease ◽  
Allergic Airway Disease

scholarly journals AscarisLarval Infection and Lung Invasion Directly Induce Severe Allergic Airway Disease in Mice

2018 ◽  
Vol 86 (12) ◽  
Author(s):  
Jill E. Weatherhead ◽  
Paul Porter ◽  
Amy Coffey ◽  
Dana Haydel ◽  
Leroy Versteeg ◽  
...  
Keyword(s):  
Airway Remodeling ◽  
Periodic Acid ◽  
Airway Disease ◽  
Allergic Airway Disease ◽  
Interleukin 4 ◽  
Lung Pathology ◽  
Periodic Acid Schiff ◽  
Content Type ◽  
Larval Migration

ABSTRACTAscaris lumbricoides(roundworm) is the most common helminth infection globally and a cause of lifelong morbidity that may include allergic airway disease, an asthma phenotype. We hypothesize thatAscarislarval migration through the lungs leads to persistent airway hyperresponsiveness (AHR) and type 2 inflammatory lung pathology despite resolution of infection that resembles allergic airway disease. Mice were infected withAscarisby oral gavage. Lung AHR was measured by plethysmography and histopathology with hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) stains, and cytokine concentrations were measured by using Luminex Magpix.Ascaris-infected mice were compared to controls or mice with allergic airway disease induced by ovalbumin (OVA) sensitization and challenge (OVA/OVA).Ascaris-infected mice developed profound AHR starting at day 8 postinfection (p.i.), peaking at day 12 p.i. and persisting through day 21 p.i., despite resolution of infection, which was significantly increased compared to controls and OVA/OVA mice.Ascaris-infected mice had a robust type 2 cytokine response in both the bronchoalveolar lavage (BAL) fluid and lung tissue, similar to that of the OVA/OVA mice, including interleukin-4 (IL-4) (P < 0.01 andP< 0.01, respectively), IL-5 (P < 0.001 andP < 0.001), and IL-13 (P < 0.001 andP < 0.01), compared to controls. By histopathology,Ascaris-infected mice demonstrated early airway remodeling similar to, but more profound than, that in OVA/OVA mice. We found thatAscarislarval migration causes significant pulmonary damage, including AHR and type 2 inflammatory lung pathology that resembles an extreme form of allergic airway disease. Our findings indicate that ascariasis may be an important cause of allergic airway disease in regions of endemicity.

scholarly journals Does unified allergic airway disease impact on lung function and type 2 biomarkers?

2019 ◽  
Vol 15 (1) ◽  
Author(s):  
Chris RuiWen Kuo ◽  
Rory Chan ◽  
Brian Lipworth
Keyword(s):  
Allergic Rhinitis ◽  
Lung Function ◽  
Allergic Asthma ◽  
Asthma Control ◽  
Persistent Asthma ◽  
Airway Disease ◽  
Allergic Airway Disease ◽  
Positive Skin Prick Test ◽  
Positive Skin

AbstractThe concept of the unified allergic airway disease (UAD) recognises the association between allergic inflammation in the upper and lower airways. Patients with asthma and concomitant allergic rhinitis experience more asthma-related primary and secondary care visits. We therefore aimed to determine differences in asthma control (asthma control questionnaire ACQ-6), lung function (spirometry) and T2 biomarkers (FeNO and Eos) in relation to the presence of allergic rhinitis in patients with allergic asthma. Retrospectively, we evaluated a cohort of 60 consecutive patients with persistent asthma attending our research unit for screening into clinical trials. All included subjects were receiving inhaled corticosteroids (ICS) and had a positive skin prick test (SPT) to at least one common aeroallergen to fulfil the criterion of allergic asthma. Patients with UAD had a diagnosis of allergic asthma in addition to established concomitant allergic rhinitis. T2 biomarkers were significantly higher in patients with allergic rhinitis in contrast to those without. FEV1 % predicted and FEF25-75 % predicted were also significantly lower in patients with concomitant allergic rhinitis. However, there was no difference in ACQ-6 observed between groups. In summary, patients with allergic asthma, the presence of concomitant allergic rhinitis is associated with worse lung function and higher type 2 biomarkers.

scholarly journals Distinct functions of tissue-resident and circulating memory Th2 cells in allergic airway disease

2020 ◽  
Vol 217 (9) ◽  
Author(s):  
Rod A. Rahimi ◽  
Keshav Nepal ◽  
Murat Cetinbas ◽  
Ruslan I. Sadreyev ◽  
Andrew D. Luster
Keyword(s):  
Allergic Asthma ◽  
Lung Parenchyma ◽  
Airway Disease ◽  
Gene Signature ◽  
Allergic Airway Disease ◽  
Transcriptional Analysis ◽  
Th2 Cells ◽  
Perivascular Inflammation

Memory CD4+ T helper type 2 (Th2) cells drive allergic asthma, yet the mechanisms whereby tissue-resident memory Th2 (Th2 Trm) cells and circulating memory Th2 cells collaborate in vivo remain unclear. Using a house dust mite (HDM) model of allergic asthma and parabiosis, we demonstrate that Th2 Trm cells and circulating memory Th2 cells perform nonredundant functions. Upon HDM rechallenge, circulating memory Th2 cells trafficked into the lung parenchyma and ignited perivascular inflammation to promote eosinophil and CD4+ T cell recruitment. In contrast, Th2 Trm cells proliferated near airways and induced mucus metaplasia, airway hyperresponsiveness, and airway eosinophil activation. Transcriptional analysis revealed that Th2 Trm cells and circulating memory Th2 cells share a core Th2 gene signature but also exhibit distinct transcriptional profiles. Th2 Trm cells express a tissue-adaptation signature, including genes involved in regulating and interacting with extracellular matrix. Our findings demonstrate that Th2 Trm cells and circulating memory Th2 cells are functionally and transcriptionally distinct subsets with unique roles in promoting allergic airway disease.

Sign in / Sign up

Export Citation Format

Share Document