Journal ArticleDOI
The immunology of asthma
Bart N. Lambrecht,Hamida Hammad +1 more
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TLDR
Results from in-depth molecular studies of mouse models in light of the results from the first clinical trials targeting key cytokines in humans are discussed and the extraordinary heterogeneity of asthma is described.Abstract:
Asthma is a common disease that affects 300 million people worldwide. Given the large number of eosinophils in the airways of people with mild asthma, and verified by data from murine models, asthma was long considered the hallmark T helper type 2 (T(H)2) disease of the airways. It is now known that some asthmatic inflammation is neutrophilic, controlled by the T(H)17 subset of helper T cells, and that some eosinophilic inflammation is controlled by type 2 innate lymphoid cells (ILC2 cells) acting together with basophils. Here we discuss results from in-depth molecular studies of mouse models in light of the results from the first clinical trials targeting key cytokines in humans and describe the extraordinary heterogeneity of asthma.read more
Citations
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Journal ArticleDOI
Regulatory T cells in allergic diseases.
TL;DR: Current concepts and established mechanisms regarding how Treg cells regulate different components of allergen-triggered immune responses to promote and maintain tolerance are reviewed to highlight opportunities for novel therapeutic strategies that aim to re-establish tolerance in patients with chronic allergic diseases.
Journal ArticleDOI
T-helper cell type 2 (Th2) and non-Th2 molecular phenotypes of asthma using sputum transcriptomics in U-BIOPRED
Chih-Hsi Scott Kuo,Chih-Hsi Scott Kuo,Stelios Pavlidis,Matthew J. Loza,F. Baribaud,Anthony Rowe,Iaonnis Pandis,Ana C. A. Sousa,Julie Corfield,Julie Corfield,Ratko Djukanovic,René Lutter,Peter J. Sterk,C. Auffray,C. Auffray,Yike Guo,Ian M. Adcock,Kian Fan Chung +17 more
TL;DR: The objective was to determine molecular phenotypes of asthma by analysing sputum cell transcriptomics from 104 moderate-to-severe asthmatic subjects and 16 nonasthmatic subjects, finding one Th2-high eosinophilic phenotype TAC1, and two non-Th2 phenotypes TAC2 and TAC3, characterised by inflammasome-associated and metabolic/mitochondrial pathways, respectively.
Journal ArticleDOI
Perinatal Activation of the Interleukin-33 Pathway Promotes Type 2 Immunity in the Developing Lung
Ismé de Kleer,Mirjam Kool,Marjolein J. W. de Bruijn,Monique Willart,Justine Van Moorleghem,Martijn J. Schuijs,Maud Plantinga,Maud Plantinga,Rudi Beyaert,Emily Hams,Padraic G. Fallon,Hamida Hammad,Rudi W. Hendriks,Bart N. Lambrecht,Bart N. Lambrecht +14 more
TL;DR: Enhanced neonatal Th2 cell skewing to inhaled allergens results from postnatal hyperactivity of the IL-33 axis during a period of maximal lung remodeling.
Journal ArticleDOI
Group 2 innate lymphoid cells license dendritic cells to potentiate memory TH2 cell responses
Timotheus Y.F. Halim,You Yi Hwang,Seth T. Scanlon,Habib Zaghouani,Natalio Garbi,Padraic G. Fallon,Padraic G. Fallon,Andrew N. J. McKenzie +7 more
TL;DR: It is demonstrated that group 2 innate lymphoid (ILC2) cells have a crucial role in memory TH2 cell responses, with targeted depletion of ILC2 cells profoundly impairing Th2 cell localization to the lungs and skin of sensitized mice after allergen re-challenge.
Journal ArticleDOI
Pulmonary neuroendocrine cells amplify allergic asthma responses
Pengfei Sui,Pengfei Sui,Darin L. Wiesner,Jinhao Xu,Jinhao Xu,Yan Zhang,Yan Zhang,Jinwoo Lee,Steven J. Van Dyken,Amber J. Lashua,Chuyue Yu,Bruce S. Klein,Richard M. Locksley,Gail H. Deutsch,Xin Sun,Xin Sun +15 more
TL;DR: In vitro data show that pulmonary neuroendocrine cells (PNECs), a rare airway epithelial cell population, can act as chemosensors, and the underlying mechanisms by identifying molecular effectors and cellular targets of PNECs are elucidated.
References
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Journal ArticleDOI
Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma
Douglas S. Robinson,Qutayba Hamid,Sun Ying,Anne Tsicopoulos,J. Barkans,Andrew Bentley,Christopher Corrigan,Stephen R. Durham,A. B. Kay +8 more
TL;DR: Atopic asthma is associated with activation in the bronchi of the interleukin-3, 4, and 5 and GM-CSF gene cluster, a pattern compatible with predominant activation of the TH2-like T-cell population.
Journal ArticleDOI
Interleukin-13: Central Mediator of Allergic Asthma
Marsha Wills-Karp,Jackie Luyimbazi,Xueying Xu,Brian Schofield,Tamlyn Neben,Christopher L. Karp,Debra D. Donaldson +6 more
TL;DR: In this paper, the type 2 cytokine IL-13, which shares a receptor component and signaling pathways with IL-4, was found to be necessary and sufficient for the expression of allergic asthma.
Journal ArticleDOI
Eosinophilic inflammation in asthma.
Jean Bousquet,Pascal Chanez,J.-Y. Lacoste,G. Barneon,N Ghavanian,I. Enander,Per Venge,Staffan Ahlstedt,J Simony-Lafontaine,P. Godard +9 more
TL;DR: Eosinophilic inflammation of the airways is correlated with the severity of asthma and these cells are likely to play a part in the epithelial damage seen in this disease.
Journal Article
Interleukin-13: Central mediator of allergic asthma
Marsha Wills-Karp,Jackie Luyimbazi,Xueying Xu,Brian Schofield,Tamlyn Neben,Christopher L. Karp,Debra D. Donaldson +6 more
TL;DR: In this article, the type 2 cytokine IL-13, which shares a receptor component and signaling pathways with IL-4, was found to be necessary and sufficient for the expression of allergic asthma.
Journal ArticleDOI
Asthma phenotypes: the evolution from clinical to molecular approaches
TL;DR: Ongoing studies of large-scale, molecularly and genetically focused and extensively clinically characterized cohorts of asthma should enhance the ability to molecularly understand these phenotypes and lead to more targeted and personalized approaches to asthma therapy.
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