Airway Remodeling Is Absent in CCR1−/− Mice During Chronic Fungal Allergic Airway 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.

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

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00056.2007 ◽

2007 ◽

Vol 293 (3) ◽

pp. L730-L739 ◽

Cited By ~ 22

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.

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Prolonged ozone exposure in an allergic airway disease model: Adaptation of airway responsiveness and airway remodeling

Respiratory Research ◽

10.1186/1465-9921-7-24 ◽

2006 ◽

Vol 7 (1) ◽

Cited By ~ 12

Author(s):

An-Soo Jang ◽

Inseon-S Choi ◽

Jae-Hyuk Lee ◽

Chang-Soo Park ◽

Choon-Sik Park

Keyword(s):

Airway Remodeling ◽

Disease Model ◽

Airway Disease ◽

Airway Responsiveness ◽

Allergic Airway Disease ◽

Ozone Exposure ◽

Model Adaptation

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

Infection and Immunity ◽

10.1128/iai.00533-18 ◽

2018 ◽

Vol 86 (12) ◽

Cited By ~ 11

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.

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Endogenous Relaxin Regulates Collagen Deposition in an Animal Model of Allergic Airway Disease

Endocrinology ◽

10.1210/en.2005-1006 ◽

2006 ◽

Vol 147 (2) ◽

pp. 754-761 ◽

Cited By ~ 41

Author(s):

Ishanee Mookerjee ◽

Natasha R. Solly ◽

Simon G. Royce ◽

Geoffrey W. Tregear ◽

Chrishan S. Samuel ◽

...

Keyword(s):

Animal Model ◽

Matrix Metalloproteinase ◽

Gene Knockout ◽

Airway Remodeling ◽

Critical Role ◽

Peptide Hormone ◽

Airway Disease ◽

Allergic Airway Disease ◽

Matrix Metalloproteinase 2 ◽

Collagen Deposition

We examined the relationship among relaxin (a peptide hormone that stimulates collagen degradation), airway fibrosis, other changes of airway remodeling, and airway hyperresponsiveness (AHR) in an animal model of allergic airway disease. Eight- to 10-wk-old relaxin gene-knockout (RLX−/−) and wild-type (RLX+/+) mice were sensitized with ovalbumin (OVA) or saline ip at d 0 and 14 and challenged three times per week for 6 wk with nebulized 2.5% OVA or saline. Saline-treated control RLX+/+ and RLX−/− mice had equivalent collagen expression and baseline airway responses. OVA-treated RLX−/− mice developed airway inflammation equivalent to that in OVA-treated RLX+/+ mice. However, OVA-treated RLX−/− mice had markedly increased lung collagen deposition as compared with OVA-treated RLX+/+ and saline-treated mice (all P < 0.05). Collagen was predominantly deposited in the subepithelial basement membrane region and submucosal regions in both OVA-treated RLX+/+ and RLX−/− mice. The increased collagen measured in OVA-treated RLX−/− mice was associated with reduced matrix metalloproteinase (MMP)-9 (P < 0.02) expression and failure to up-regulate matrix metalloproteinase-2 expression, compared with levels in OVA-treated RLX+/+ mice. Goblet cell numbers were equivalent in OVA-treated RLX−/− and RLX+/+ mice and increased, compared with saline-treated animals. Both OVA-treated RLX+/+ and RLX−/− mice developed similar degrees of AHR after OVA treatment. These findings demonstrate a critical role for relaxin in the inhibition of lung collagen deposition during an allergic inflammatory response. Increased deposition of collagen per se did not influence airway epithelial structure or AHR.

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Long-term exposure to low-dose Haemophilus influenzae during allergic airway disease drives a steroid-resistant neutrophilic inflammation and promotes airway remodeling

Oncotarget ◽

10.18632/oncotarget.24653 ◽

2018 ◽

Vol 9 (38) ◽

pp. 24898-24913 ◽

Cited By ~ 2

Author(s):

Xu Yang ◽

Yijie Wang ◽

Shengtao Zhao ◽

Ran Wang ◽

Changzheng Wang

Keyword(s):

Haemophilus Influenzae ◽

Low Dose ◽

Airway Remodeling ◽

Airway Disease ◽

Allergic Airway Disease ◽

Steroid Resistant ◽

Neutrophilic Inflammation

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CXCL12 Inhibition Attenuates Pericyte Mobilization and Ameliorates Airway Remodeling in Chronic Allergic Airway Disease

10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a5605 ◽

2020 ◽

Author(s):

J. Johnson ◽

R.E. Bignold

Keyword(s):

Airway Remodeling ◽

Airway Disease ◽

Allergic Airway Disease

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Airway Remodeling In House Dust Mite-Induced Allergic Airway Disease

10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a5401 ◽

2012 ◽

Author(s):

Jos L.J. van der Velden ◽

Lennart K.A. Lundblad ◽

Shannon Li ◽

Minara Aliyeva ◽

Nirav Daphtary ◽

...

Keyword(s):

House Dust ◽

House Dust Mite ◽

Airway Remodeling ◽

Airway Disease ◽

Allergic Airway Disease ◽

Dust Mite

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Regulatory T cells mediated immunomodulation during asthma: a therapeutic standpoint

Journal of Translational Medicine ◽

10.1186/s12967-020-02632-1 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Mohammad Afzal Khan

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Airway Inflammation ◽

Therapeutic Potential ◽

Airway Remodeling ◽

Clinical Manifestations ◽

Inflammatory Cells ◽

Airway Disease ◽

Vital Role ◽

Allergic Airway Disease

AbstractAsthma is an inflammatory disease of the lung airway network, which is initiated and perpetuated by allergen-specific CD4+ T cells, IgE antibodies, and a massive release of Th2 cytokines. The most common clinical manifestations of asthma progression include airway inflammation, pathological airway tissue and microvascular remodeling, which leads to airway hyperresponsiveness (AHR), and reversible airway obstruction. In addition to inflammatory cells, a tiny population of Regulatory T cells (Tregs) control immune homeostasis, suppress allergic responses, and participate in the resolution of inflammation-associated tissue injuries. Preclinical and clinical studies have demonstrated a tremendous therapeutic potential of Tregs in allergic airway disease, which plays a crucial role in immunosuppression, and rejuvenation of inflamed airways. These findings supported to harness the immunotherapeutic potential of Tregs to suppress airway inflammation and airway microvascular reestablishment during the progression of the asthma disease. This review addresses the therapeutic impact of Tregs and how Treg mediated immunomodulation plays a vital role in subduing the development of airway inflammation, and associated airway remodeling during the onset of disease.

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