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.

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.

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 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 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.

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

2002 ◽  
Vol 283 (1) ◽  
pp. L198-L204 ◽  
Author(s):  
Jane M. Schuh ◽  
Kate Blease ◽  
Steven L. Kunkel ◽  
Cory M. Hogaboam
Keyword(s):  
T Cell ◽  
Airway Hyperresponsiveness ◽  
Airway Disease ◽  
Allergic Airway Disease ◽  
Th2 Cells ◽  
Wild Type ◽  
Cell Recruitment ◽  
Chronic Model ◽  
Airway Responses

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.

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 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 Inhaled house dust programs pulmonary dendritic cells to promote type 2 T-cell responses by an indirect mechanism

2015 ◽  
Vol 309 (10) ◽  
pp. L1208-L1218 ◽  
Author(s):  
Timothy P. Moran ◽  
Keiko Nakano ◽  
Gregory S. Whitehead ◽  
Seddon Y. Thomas ◽  
Donald N. Cook ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Allergic Asthma ◽  
House Dust ◽  
Lavage Fluid ◽  
Th2 Cells ◽  
T Helper 2 ◽  
Cell Responses ◽  
Th2 Responses ◽  
Th2 Differentiation

The induction of allergen-specific T helper 2 (Th2) cells by lung dendritic cells (DCs) is a critical step in allergic asthma development. Airway delivery of purified allergens or microbial products can promote Th2 priming by lung DCs, but how environmentally relevant quantities and combinations of these factors affect lung DC function is unclear. Here, we investigated the ability of house dust extract (HDE), which contains a mixture of environmental adjuvants, to prime Th2 responses against an innocuous inhaled antigen. Inhalational exposure to HDE conditioned lung conventional DCs, but not monocyte-derived DCs, to induce antigen-specific Th2 differentiation. Conditioning of DCs by HDE was independent of Toll-like receptor 4 signaling, indicating that environmental endotoxin is dispensable for programming DCs to induce Th2 responses. DCs directly treated with HDE underwent maturation but were poor stimulators of Th2 differentiation. In contrast, DCs treated with bronchoalveolar lavage fluid (BALF) from HDE-exposed mice induced robust Th2 differentiation. DC conditioning by BALF was independent of the proallergic cytokines IL-25, IL-33, and thymic stromal lymphopoietin. BALF treatment of DCs resulted in upregulation of CD80 but low expression of CD40, CD86, and IL-12p40, which was associated with Th2 induction. These findings support a model whereby environmental adjuvants in house dust indirectly program DCs to prime Th2 responses by triggering the release of endogenous soluble factor(s) by airway cells. Identifying these factors could lead to novel therapeutic targets for allergic asthma.

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