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
15-Deoxy-Delta-12,14-Prostaglandin J2 Inhibits Lung Inflammation and Remodeling in Distinct Murine Models of Asthma.
Diego de Sá Coutinho,Edna A. Anjos-Valotta,Caio Victor M. F. do Nascimento,Ana Lucia A. Pires,Marcelo H. Napimoga,Vinicius F. Carvalho,Rafael Carvalho Torres,Patrícia M.R. e Silva,Marco A. Martins +8 more
TL;DR: It is suggested that 15d-PGJ2 can reduce crucial features of asthma, including AHR, lung inflammation, and remodeling in distinct murine models of the disease by a mechanism related to downregulation of NF-κB phosphorylation.
Journal ArticleDOI
Lung-restricted inhibition of Janus kinase 1 is effective in rodent models of asthma.
Hart S. Dengler,Xiumin Wu,Ivan Peng,Cornelia H. Rinderknecht,Youngsu Kwon,Eric Suto,Pawan Bir Kohli,Marya Liimatta,Kathy Barrett,Julia Lloyd,Gary Cain,Mike Briggs,Stephanie Addo,Gary Salmon,Savita Ubhayakar,Gauri Deshmukh,Sheerin K. Shahidi-Latham,Cristine M. Quiason-Huynh,Janet Jackman,John Liu,Nicholas Charles Ray,Simon Charles Goodacre,Adam R. Johnson,Brent S. McKenzie,Wyne P. Lee,Mark Zak,Jane R. Kenny,Nico Ghilardi +27 more
TL;DR: The data show that local inhibition of Jak1 in the lung can suppress lung inflammation without systemic Jak inhibition in rodents, suggesting that this strategy might be effective for treating asthma.
Journal ArticleDOI
Protein kinase Cθ controls type 2 innate lymphoid cell and TH2 responses to house dust mite allergen
Fahima Madouri,Pauline Chenuet,Chloé Beuraud,Louis Fauconnier,Tiffany Marchiol,Nathalie Rouxel,Aurélie Ledru,Margaux Gallerand,Vincent Lombardi,Laurent Mascarell,Quentin Marquant,Lionel Apetoh,François Erard,Marc Le Bert,Fabrice Trovero,Valérie F. J. Quesniaux,Bernhard Ryffel,Bernhard Ryffel,Dieudonnée Togbe +18 more
TL;DR: Findings identify PKC‐&THgr; as a critical factor for ILC2 activation that contributes to TH2 cell differentiation, which is associated with IRF4 and NFAT1 expression in allergic lung inflammation.
Journal ArticleDOI
Immunomodulatory innate defence regulator (IDR) peptide alleviates airway inflammation and hyper-responsiveness.
Hadeesha Piyadasa,Mahadevappa Hemshekhar,Anthony Altieri,Sujata Basu,Sujata Basu,Anne M. van der Does,Andrew J. Halayko,Pieter S. Hiemstra,Neeloffer Mookherjee +8 more
TL;DR: This study demonstrates that an immunomodulatory IDR peptide controls the pathophysiology of asthma in a murine model, and significantly reduced either HDM, IL-33 or HDM+IL-33 co-challenge-induced AHR in vivo.
Journal ArticleDOI
Inhibition of the Inflammasome Activity of NLRP3 Attenuates HDM-Induced Allergic Asthma.
TL;DR: In this article, the authors showed that inhaled house dust mite (HDM) promotes NLRP3 inflammasome activation in the lungs and specifically induces the maturation of caspase-1 and IL-1β in alveolar macrophages (AMs).
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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