IL-25 Receptor Expression on Airway Dendritic Cells after Allergen Challenge in Subjects with Asthma

Tworek, Damian; Smith, Steven G; Salter, Brittany; Baatjes, Adrian J; Scime, Tara; Watson, Rick; Obminski, Caitlin; Gauvreau, Gail M.; O’Byrne, Paul M.

doi:10.1164/rccm.201509-1751oc

Cited by 47 publications

(43 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The effects of airway allergen challenge on IL-17RB expression by dendritic cells (DCs) is the subject of the article in this issue of the Journal by Tworek and colleagues (pp. 957-964) (17). These authors find that both myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) express IL-17RB and that both DC subsets increase in the airway after allergen challenge, coincident with increases in airway eosinophils and nitric oxide levels and with decrements in lung function.…”

Section: Cross-talk Between Epithelial Cells and Type 2 Immune Signalingmentioning

confidence: 99%

“…Ultimately, it may emerge that tissue differences in expression levels of these three cytokines will dictate therapeutic approaches for cytokine inhibitors in tissue-specific diseases, such as asthma, eosinophilic esophagitis, or nasal polyposis. Alternatively, regulation of cytokine receptors, as revealed in the manuscript by Tworek and colleagues (17), may provide critical insights on the best approaches for intervention. Ultimately, clinical trials will be needed to answer these questions, as well as those related to safety and potential off-target effects.…”

Section: Cross-talk Between Epithelial Cells and Type 2 Immune Signalingmentioning

confidence: 99%

See 1 more Smart Citation

Cross-Talk between Epithelial Cells and Type 2 Immune Signaling. The Role of IL-25

Gordon¹,

Locksley

Fahy³

2016

Am J Respir Crit Care Med

View full text Add to dashboard Cite

Section: Cross-talk Between Epithelial Cells and Type 2 Immune Signalingmentioning

confidence: 99%

Section: Cross-talk Between Epithelial Cells and Type 2 Immune Signalingmentioning

confidence: 99%

Cross-Talk between Epithelial Cells and Type 2 Immune Signaling. The Role of IL-25

Gordon¹,

Locksley

Fahy³

2016

Am J Respir Crit Care Med

View full text Add to dashboard Cite

“…Levels of this receptor are increased on the surfaces of both myeloid and plasmacytoid DCs in the airways of patients with mild asthma after allergen challenge. 64 IL-25 coordinates with TSLP-activated human DCs to induce T H 2 polarization and augment T H 2 responses by enhancing expression of genes encoding T H 2-associated transcription factors ( GATA3 , c-MAF , and JUNB ), increasing expression of T H 2 signature surface markers (CCR4 and IL-4R) and maintaining chemoattractant receptor–homologous molecule expressed on T H 2 lymphocytes (CRTH2; Figs 1, B , and 2). IL-25 also sustains expression of transcription factors and augments production of IL-5 and IL-13 in an IL-4–independent manner through direct T-cell effects.…”

Section: Tslpmentioning

confidence: 99%

Pathogenic CD4 + T cells in patients with asthma

Muehling

Lawrence

Woodfolk

2017

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

Asthma encompasses a variety of clinical phenotypes that involve distinct T cell–driven inflammatory processes. Improved understanding of human T-cell biology and the influence of innate cytokines on T-cell responses at the epithelial barrier has led to new asthma paradigms. This review captures recent knowledge on pathogenic CD4+ T cells in asthmatic patients by drawing on observations in mouse models and human disease. In patients with allergic asthma, TH2 cells promote IgE-mediated sensitization, airway hyperreactivity, and eosinophilia. Here we discuss recent discoveries in the myriad molecular pathways that govern the induction of TH2 differentiation and the critical role of GATA-3 in this process. We elaborate on how cross-talk between epithelial cells, dendritic cells, and innate lymphoid cells translates to T-cell outcomes, with an emphasis on the actions of thymic stromal lymphopoietin, IL-25, and IL-33 at the epithelial barrier. New concepts on how T-cell skewing and epitope specificity are shaped by multiple environmental cues integrated by dendritic cell “hubs” are discussed. We also describe advances in understanding the origins of atypical TH2 cells in asthmatic patients, the role of TH1 cells and other non-TH2 types in asthmatic patients, and the features of T-cell pathogenicity at the single-cell level. Progress in technologies that enable highly multiplexed profiling of markers within a single cell promise to overcome barriers to T-cell discovery in human asthmatic patients that could transform our understanding of disease. These developments, along with novel T cell–based therapies, position us to expand the assortment of molecular targets that could facilitate personalized treatments.

show abstract

“…However, these effects are largely dependent on the ability of IL-25 to induce IL-13. Consistent with this, allergen exposure has been shown to upregulate IL-25R (IL-17RB) on dendritic cells in asthmatics [76]. IL-25 has been show to activate DCs by upregulation of co-stimulatory molecule expression (CD80, CD86) [77] and Jagged-1 [78], which promotes the differentiation of naïve T cells into Th2 lineage.…”

Section: Introductionmentioning

confidence: 91%

Epithelial Cell Regulation of Allergic Diseases

Gour

Lajoie

2016

Curr Allergy Asthma Rep

View full text Add to dashboard Cite

Allergic diseases, which have escalated in prevalence in recent years, arise as a result of maladaptive immune responses to ubiquitous environmental stimuli. Why only certain individuals mount inappropriate type 2 immune responses to these otherwise harmless allergens has remained an unanswered question. Mounting evidence suggests that the epithelium, by sensing its environment, is the central regulator of allergic diseases. Once considered to be a passive barrier to allergens, epithelial cells at mucosal surfaces are now considered to be the cornerstone of the allergic diathesis. Beyond their function as maintaining barrier at mucosal surfaces, mucosal epithelial cells through the secretion of mediators like IL-25, IL-33, and TSLP control the fate of downstream allergic immune responses. In this review, we will discuss the advances in recent years regarding the process of allergen recognition and secretion of soluble mediators by epithelial cells that shape the development of the allergic response.

show abstract

IL-25 Receptor Expression on Airway Dendritic Cells after Allergen Challenge in Subjects with Asthma

Abstract: IL-17RB is up-regulated on blood and sputum mDCs and pDCs after allergen inhalation. IL-25 modulates pDC function through an effect on TLR9 expression.

Cited by 47 publications

References 28 publications

Cross-Talk between Epithelial Cells and Type 2 Immune Signaling. The Role of IL-25

Cross-Talk between Epithelial Cells and Type 2 Immune Signaling. The Role of IL-25

Pathogenic CD4 + T cells in patients with asthma

Epithelial Cell Regulation of Allergic Diseases

Contact Info

Product

Resources

About