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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Eighty-eight variants highlight the role of T cell regulation and airway remodeling in asthma pathogenesis
Thorunn A. Olafsdottir,Thorunn A. Olafsdottir,Fannar Theodors,Kristbjorg Bjarnadottir,Unnur S. Bjornsdottir,Arna B Agustsdottir,Olafur A. Stefansson,Erna V. Ivarsdottir,Erna V. Ivarsdottir,Jon K. Sigurdsson,Stefania Benonisdottir,Gudmundur I. Eyjolfsson,David Gislason,Thorarinn Gislason,Steinunn Guðmundsdóttir,Arnaldur Gylfason,Bjarni V. Halldorsson,Bjarni V. Halldorsson,Gisli H. Halldorsson,Thorhildur Juliusdottir,Anna M. Kristinsdottir,Dora Ludviksdottir,Dora Ludviksdottir,Bjorn R. Ludviksson,Bjorn R. Ludviksson,Gisli Masson,Kristjan Norland,Pall T. Onundarson,Isleifur Olafsson,Olof Sigurdardottir,Lilja Stefansdottir,Gardar Sveinbjornsson,Vinicius Tragante,Vinicius Tragante,Daniel F. Gudbjartsson,Daniel F. Gudbjartsson,Gudmar Thorleifsson,Patrick Sulem,Unnur Thorsteinsdottir,Unnur Thorsteinsdottir,Gudmundur L. Norddahl,Ingileif Jonsdottir,Ingileif Jonsdottir,Kari Stefansson,Kari Stefansson +44 more
TL;DR: A genome-wide meta-analysis of two large population-based cohorts is reported to identify sequence variants that associate with asthma risk and perform follow-up functional analyses on a protective loss-of-function variant in TNFRSF8.
Journal ArticleDOI
NLRP3 regulates macrophage M2 polarization through up-regulation of IL-4 in asthma
Ying Liu,Xin Gao,Yi Miao,Wang Yuanyuan,Huan Wang,Zhe Cheng,Xi Wang,Xiaogang Jing,Liuqun Jia,Lingling Dai,Meng Liu,Lin An +11 more
TL;DR: NLRP3, but not the inflammasome adaptor ASC or caspase-1, promoted the polarization of M2 macrophages through up-regulating the expression of IL-4, thereby contributing to its regulation of asthma.
Journal ArticleDOI
Lung CD103+ dendritic cells restrain allergic airway inflammation through IL-12 production
Laura Conejero,Sofía C. Khouili,Sarai Martínez-Cano,Helena M. Izquierdo,Paola Brandi,David Sancho +5 more
TL;DR: In vivo IL-12 treatment reverts exacerbated allergic airway inflammation upon chronic HDM challenge in Batf3-/- mice, restraining Th2 and Th17 responses without triggering Th1 immunity, suggesting a protective role for lung CD103+ DCs to HDM allergicAirway inflammation through the production of IL- 12.
Journal ArticleDOI
New insights in neutrophilic asthma.
TL;DR: Research of the last few years has accelerated the insights in mechanisms underlying neutrophilic asthma, in stark contrast with the lack of efficacy of different therapies targeting neutrophil chemotaxis and/or signalling cascade, such as IL-17A or CXCR2.
Journal ArticleDOI
Eosinophil recruitment is dynamically regulated by interplay among lung dendritic cell subsets after allergen challenge
Shuying Yi,Jing Zhai,Rui Niu,Guangming Zhu,Meixiang Wang,Jianguo Liu,Hua Huang,Yaping Wang,Xiuli Jing,Li Kang,Wengang Song,Yufang Shi,Hua Tang +12 more
TL;DR: The data suggest that different lung antigen-presenting cells modulate lung cDC1-mediated eosinophil recruitment dynamically, through secreting distinct soluble factors during the memory stage of chronic asthma after allergen challenge in the mouse.
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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