scholarly journals Butyrate Shapes Immune Cell Fate and Function in Allergic Asthma

2021 ◽  
Vol 12 ◽  
Author(s):  
William Yip ◽  
Michael R. Hughes ◽  
Yicong Li ◽  
Alissa Cait ◽  
Martin Hirst ◽  
...  
Keyword(s):  
Allergic Asthma ◽  
Cell Fate ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Regulation Of Gene Expression ◽  
Airway Disease ◽  
Short Chain Fatty Acids ◽  
Allergic Airway Disease ◽  
Intestinal Microbiome ◽  
And Function

The microbiome plays a fundamental role in how the immune system develops and how inflammatory responses are shaped and regulated. The “gut-lung axis” is a relatively new term that highlights a crucial biological crosstalk between the intestinal microbiome and lung. A growing body of literature suggests that dysbiosis, perturbation of the gut microbiome, is a driving force behind the development, and severity of allergic asthma. Animal models have given researchers new insights into how gut microbe-derived components and metabolites, such as short-chain fatty acids (SCFAs), influence the development of asthma. While the full understanding of how SCFAs influence allergic airway disease remains obscure, a recurring theme of epigenetic regulation of gene expression in several immune cell compartments is emerging. This review will address our current understanding of how SCFAs, and specifically butyrate, orchestrates cell behavior, and epigenetic changes and will provide a detailed overview of the effects of these modifications on immune cells in the context of allergic airway disease.

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 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 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 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 How immune‐cell fate and function are determined by metabolic pathway choice

BioEssays ◽  
2020 ◽  
pp. 2000067
Author(s):  
Marcela Hortová‐Kohoutková ◽  
Petra Lázničková ◽  
Jan Frič
Keyword(s):  
Cell Fate ◽  
Metabolic Pathway ◽  
Immune Cell ◽  
Pathway Choice ◽  
And Function

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.

scholarly journals Cellular senescence impact on immune cell fate and function

Aging Cell ◽  
2016 ◽  
Vol 15 (3) ◽  
pp. 400-406 ◽  
Author(s):  
Rita Vicente ◽  
Anne-Laure Mausset-Bonnefont ◽  
Christian Jorgensen ◽  
Pascale Louis-Plence ◽  
Jean-Marc Brondello
Keyword(s):  
Cell Fate ◽  
Cellular Senescence ◽  
Immune Cell ◽  
And Function

scholarly journals Identification of Axl as a downstream effector of TGF-β1 during Langerhans cell differentiation and epidermal homeostasis

2012 ◽  
Vol 209 (11) ◽  
pp. 2033-2047 ◽  
Author(s):  
Thomas Bauer ◽  
Anna Zagórska ◽  
Jennifer Jurkin ◽  
Nighat Yasmin ◽  
René Köffel ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Apoptotic Cell ◽  
Skin Inflammation ◽  
Transforming Growth Factor Β1 ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
And Function ◽  
Tgf Β1

Transforming growth factor-β1 (TGF-β1) is a fundamental regulator of immune cell development and function. In this study, we investigated the effects of TGF-β1 on the differentiation of human Langerhans cells (LCs) and identified Axl as a key TGF-β1 effector. Axl belongs to the TAM (Tyro3, Axl, and Mer) receptor tyrosine kinase family, whose members function as inhibitors of innate inflammatory responses in dendritic cells and are essential to the prevention of lupus-like autoimmunity. We found that Axl expression is induced by TGF-β1 during LC differentiation and that LC precursors acquire Axl early during differentiation. We also describe prominent steady-state expression as well as inflammation-induced activation of Axl in human epidermal keratinocytes and LCs. TGF-β1–induced Axl enhances apoptotic cell (AC) uptake and blocks proinflammatory cytokine production. The antiinflammatory role of Axl in the skin is reflected in a marked impairment of the LC network preceding spontaneous skin inflammation in mutant mice that lack all three TAM receptors. Our findings highlight the importance of constitutive Axl expression to tolerogenic barrier immunity in the epidermis and define a mechanism by which TGF-β1 enables silent homeostatic clearing of ACs to maintain long-term self-tolerance.

scholarly journals Short-Chain Fatty Acids

2020 ◽  
Author(s):  
Paulina Markowiak-Kopeć ◽  
Katarzyna Śliżewska
Keyword(s):  
Fatty Acids ◽  
Volatile Fatty Acids ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Intestinal Microbiome ◽  
Test Results ◽  
And Function ◽  
The Relationship ◽  
Normal Health ◽  
Chain Fatty Acids

The relationship between diet and the diversity and function of the intestinal microbiomeand its importance for human health is currently the subject of many studies. The type and proportionof microorganisms found in the intestines can determine the energy balance of the host. Intestinalmicroorganisms perform many important functions, one of which is participation in metabolicprocesses, e.g., in the production of short-chain fatty acids—SCFAs (also called volatile fatty acids).These acids represent the main carbon flow from the diet to the host microbiome. Maintainingintestinal balance is necessary to maintain the host’s normal health and prevent many diseases.The results of many studies confirm the beneficial effect of probiotic microorganisms on the balanceof the intestinal microbiome and produced metabolites, including SCFAs. The aim of this review is tosummarize what is known on the effects of probiotics on the production of short-chain fatty acidsby gut microbes. In addition, the mechanism of formation and properties of these metabolites isdiscussed and verified test results confirming the effectiveness of probiotics in human nutrition bymodulating SCFAs production by intestinal microbiome is presented.

scholarly journals Colonic Mucosal Immune Activation in Mice with Ovalbumin-Induced Allergic Airway Disease: Association between Allergic Airway Disease and Irritable Bowel Syndrome

2021 ◽  
Vol 23 (1) ◽  
pp. 181
Author(s):  
Sanghyun Kim ◽  
Bora Keum ◽  
Junhyoung Byun ◽  
Byoungjae Kim ◽  
Kijeong Lee ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Inflammatory Response ◽  
Intestinal Mucosa ◽  
Inflammatory Responses ◽  
Airway Disease ◽  
Allergic Airway Disease ◽  
Airway Diseases ◽  
Cytokine Levels ◽  
Irritable Bowel

Recent studies on the pathophysiology of irritable bowel syndrome (IBS) have focused on the role of mast cells (MCs) in intestinal mucosal immunity. A link between allergic airway diseases (AADs) and IBS has been suggested because both diseases have similar pathophysiology. We aimed to investigate whether the induction of AAD in mice could lead to inflammation of the colonic mucosa, similar to IBS. We also evaluated whether this inflammatory response could be suppressed by administering a therapeutic agent. Mice were divided into three groups: control, AAD-induced, and salbutamol-treated. An AAD mouse model was established by intraperitoneal injection and nasal challenge with ovalbumin. Mice with AAD were intranasally administered salbutamol. Analyses of cytokine levels, MC count, and tryptase levels in the intestinal mucosa were performed to compare the changes in inflammatory responses among the three groups. Inflammation was observed in the intestinal mucosa of mice in the AAD group. This inflammation in AAD mice was suppressed after salbutamol treatment. Our study demonstrates that AAD induces an inflammatory response similar to that in IBS, suggesting a possible association between IBS and AADs. In patients with IBS with such allergic components, salbutamol may have the potential to alleviate the inflammatory response.

Sign in / Sign up

Export Citation Format

Share Document