House dust mite–driven asthma and allergen-specific T cells depend on B cells when the amount of inhaled allergen is limiting

Dullaers, Mélissa; Schuijs, Martijn J.; Willart, Monique; Fierens, Kaat; Moorleghem, Justine Van; Hammad, Hamida; Lambrecht, Bart N.

doi:10.1016/j.jaci.2016.09.020

Cited by 60 publications

(72 citation statements)

References 54 publications

(85 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The expression of Th2 cytokines in supernatants of in vitro OVA‐restimulated medLN cell cultures from WT mice was highly elevated in AAI mice and significantly reduced after egg treatment (Figure C). Allergic μMT mice produced significantly less IL‐5, IL‐10 and IL‐13 compared to their WT counterparts (Figure C), like recently also shown in a house dust mite model of asthma . As expected, OVA‐specific IgG1 and IgE antibodies in μMT mice remained at baseline values observed in naïve WT animals (Figure D), excluding a major role of inhibitory antibodies in protection.…”

Section: Resultssupporting

confidence: 79%

“…In line with these data, we also found the allergic response to be unaffected in μMT mice, apart from a significant reduction in the allergen‐specific Th2 cytokine production by medLN cells. This could be, at least in part, due to the amount of allergen used, as we have previously reported an important role for B cells in low‐dose HDM‐induced AAI . Despite the difference in OVA‐specific Th2 responses, egg treatment equally protects from AAI both in WT and μMT mice, indicating that mature B cells are not crucial for protection.…”

Section: Discussionmentioning

confidence: 86%

See 1 more Smart Citation

Isolated Schistosoma mansoni eggs prevent allergic airway inflammation

Obieglo

Schuijs

Ozir‐Fazalalikhan

et al. 2018

Parasite Immunology

Self Cite

View full text Add to dashboard Cite

SummaryChronic helminth infection with Schistosoma (S.) mansoni protects against allergic airway inflammation (AAI) in mice and is associated with reduced Th2 responses to inhaled allergens in humans, despite the presence of schistosome‐specific Th2 immunity. Schistosome eggs strongly induce type 2 immunity and allow to study the dynamics of Th2 versus regulatory responses in the absence of worms. Treatment with isolated S. mansoni eggs by i.p. injection prior to induction of AAI to ovalbumin (OVA)/alum led to significantly reduced AAI as assessed by less BAL and lung eosinophilia, less cellular influx into lung tissue, less OVA‐specific Th2 cytokines in lungs and lung‐draining mediastinal lymph nodes and less circulating allergen‐specific IgG1 and IgE antibodies. While OVA‐specific Th2 responses were inhibited, treatment induced a strong systemic Th2 response to the eggs. The protective effect of S. mansoni eggs was unaltered in μMT mice lacking mature (B2) B cells and unaffected by Treg cell depletion using anti‐CD25 blocking antibodies during egg treatment and allergic sensitization. Notably, prophylactic egg treatment resulted in a reduced influx of pro‐inflammatory, monocyte‐derived dendritic cells into lung tissue of allergic mice following challenge. Altogether, S. mansoni eggs can protect against the development of AAI, despite strong egg‐specific Th2 responses.

show abstract

Section: Resultssupporting

confidence: 79%

Section: Discussionmentioning

confidence: 86%

Isolated Schistosoma mansoni eggs prevent allergic airway inflammation

Obieglo

Schuijs

Ozir‐Fazalalikhan

et al. 2018

Parasite Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Specifically, when inhaled allergen is limiting, the enlistment of B cells as antigen-presenting cells (APCs), in addition to DCs, contributes to optimal expansion of these populations and concomitant asthma. 32 …”

Section: Th2 Differentiation and T-cell Trafficking In Asthmatic Patimentioning

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, a major criticism is the fact that OVA is a food allergen. Therefore, animal models have been adapted to airborne allergens derived from HDM …”

Section: Introductionmentioning

confidence: 99%

TLR9 agonist adsorbed to alum adjuvant prevents asthma-like responses induced by Blomia tropicalis mite extract

Nunes¹,

Alberca²,

Gomes³

et al. 2019

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Blomia tropicalis mite is highly prevalent in tropical and subtropical regions and it is associated with allergic diseases such as rhinitis and asthma. By using an OVA‐model of allergic lung disease, we have previously shown that sensitization in the presence of toll like receptors (TLRs) agonists attenuates subsequent OVA‐induced allergic responses. Here, we evaluated the effect of CpG‐ODN, a specific synthetic TLR‐9 agonist, on the development of experimental asthma induced by Blomia tropicalis extract, a relevant source of aeroallergens. Among different protocols of Blomia tropicalis extract sensitization, the subcutaneous sensitization in the presence of alum adjuvant induced the highest Th2 responses, including high IgE levels. Adsorption of CpG to Blomia tropicalis extract/Alum attenuated the airway hyperreactivity, the infiltration of inflammatory cells including eosinophils, and the IL‐5 content in BAL. In addition, lung peribronchial inflammatory infiltrate, mucus production and IL‐5‐producing CD3+CD4+ T cells were significantly reduced in the Blomia tropicalis extract/Alum+CpG group. Importantly, CpG inhibited total IgE production as well as active systemic or cutaneous anaphylaxis reactions. Inhibition of pulmonary Th2 responses was associated with increased IL‐10 production but not with IFN‐γ production. Notably, in IL‐10‐deficient mice, sensitization with OVA/Alum+CpG resulted in intense lung neutrophilia and IFN‐γ production, indicating that IL‐10 is necessary to inhibit subsequent Th1 immunity. Our work highlights the mechanisms of allergy attenuation by CpG and it indicates the potential use of Alum‐based formulation with CpG to treat allergic processes.

show abstract

House dust mite–driven asthma and allergen-specific T cells depend on B cells when the amount of inhaled allergen is limiting

Abstract: B cells are a major part of the adaptive immune response to inhaled HDM allergen, particularly when the amount of inhaled allergen is low, by expanding allergen-specific T cells.

Cited by 60 publications

References 54 publications

Isolated Schistosoma mansoni eggs prevent allergic airway inflammation

Isolated Schistosoma mansoni eggs prevent allergic airway inflammation

Pathogenic CD4 + T cells in patients with asthma

TLR9 agonist adsorbed to alum adjuvant prevents asthma-like responses induced by Blomia tropicalis mite extract

Contact Info

Product

Resources

About