Focus
Focus on Asthma
Asthma affects an estimated 300 million people worldwide. Despite the availability of therapies for symptomatic control of the disease, a significant fraction of patients remain refractory to treatment and progress to severe asthma. This series of reviews highlights recent advances in our understanding of asthma pathogenesis, clinical presentation of disease, and novel therapies aimed at targeting pathologic mechanisms initiating and sustaining allergic inflammation.
We thank Almirall and Theravance for their generous support, which has enabled us to make this collection of reviews and recently published research articles freely available to the community for a period of three months.
Editorial
Focus on Asthma
A fresh perspective on asthma
Published online: 4 May 2012 | doi:10.1038/nm.2777
Abstract - | Full Text - Tumor angiogenesis: molecular pathways and therapeutic targets | PDF (19 MB) - A fresh perspective on asthma
Reviews
Focus on Asthma
Innate and adaptive immune responses in asthma
Stephen T Holgate
doi:10.1038/nm.2731
Allergen sensitization is triggered by activating receptors of the innate arm of the immune system. This leads to the recruitment and activation of dendritic cells, which have a sentinel role in orchestrating the attendant adaptive response. Stephen Holgate highlights recent findings on how innate receptors are triggered, cellular sources of cytokines driving immune cell activation and the identification of new helper T cell subsets driving chronic allergic airway inflammation.
Abstract - | Full Text - Innate and adaptive immune responses in asthma | PDF (3,208 KB) - Innate and adaptive immune responses in asthma
Focus on Asthma
The airway epithelium in asthma
Bart N Lambrecht & Hamida Hammad
doi:10.1038/nm.2737
The airway epithelium has a sentinel role in initiating allergic responses and asthma. Bart Lambrecht and Hamida Hammad review recent findings on how allergens activate epithelial cells and induce the production of cytokines and chemokines that recruit and activate dendritic cells and other cells of the innate immune system. Activation of these cell types promotes adaptive immune responses, which are, the authors argue, further maintained and perpetuated by their interaction with airway epithelial cells.
Abstract - | Full Text - The airway epithelium in asthma | PDF (2,664 KB) - The airway epithelium in asthma
Focus on Asthma
T cell homing to epithelial barriers in allergic disease
Sabina A Islam & Andrew D Luster
doi:10.1038/nm.2760
Efficient trafficking of lymphocytes between the blood, lymphoid organs and peripheral tissues is essential for an effective immune response. Sabina Islam and Andrew Luster summarize recent findings on the regulation of leukocyte homing to the lungs, gut and skin in allergic inflammation and how leukocyte trafficking can be targeted clinically.
Abstract - | Full Text - T cell homing to epithelial barriers in allergic disease | PDF (3,411 KB) - T cell homing to epithelial barriers in allergic disease
Focus on Asthma
IgE and mast cells in allergic disease
Stephen J Galli & Mindy Tsai
doi:10.1038/nm.2755
Both mast cells and IgE play crucial parts during the initiation and amplification of the allergic response during asthma, as well as during the tissue remodeling that occurs at the chronic stage. This review discusses how these two players can affect the development of asthma through independent and interdependent functions and the therapeutic implications for treating the clinical symptoms derived from allergic disease.
Abstract - | Full Text - IgE and mast cells in allergic disease | PDF (1,565 KB) - IgE and mast cells in allergic disease
Focus on Asthma
Viral infections and atopy in asthma pathogenesis: new rationales for asthma prevention and treatment - pp726 - 735
Patrick G Holt & Peter D Sly
doi:10.1038/nm.2768
Viral infections can worsen episodes of allergic sensitization to allergens, putting the affected individuals, often children, at risk for developing persistent asthma during adult life. Understanding how the mechanisms mediating the antiviral response and driving allergic inflammation caused by allergens interact is crucial. This will provide insights into when and what player or molecule to target for treatment and prevention of asthma in children at the early stages of the disease.
Abstract - | Full Text - Viral infections and atopy in asthma pathogenesis: new rationales for asthma prevention and treatment | PDF (3,126 KB) - Viral infections and atopy in asthma pathogenesis: new rationales for asthma prevention and treatment
Focus on Asthma
Asthma phenotypes: the evolution from clinical to molecular approaches
Sally E Wenzel
doi:10.1038/nm.2678
The growing appreciation of asthma as a heterogeneous disease has led to the concept that asthma consists of multiple, different phenotypes, but now the challenge is to link underlying biology to phenotypes to allow a more robust classification and understanding of asthma. This review discusses the progress in defining asthma phenotypes and provides insights into how to apply this knowledge to provide more personalized approaches to treating asthma.
Abstract - | Full Text - Asthma phenotypes: the evolution from clinical to molecular approaches | PDF (1,112 KB) - Asthma phenotypes: the evolution from clinical to molecular approaches
Focus on Asthma
Therapies for allergic inflammation: refining strategies to induce tolerance
Cezmi A Akdis
doi:10.1038/nm.2754
This review outlines recent advances in the development of therapeutics that induce immune tolerance to treat asthma and allergic disease. It focuses on the distinct approaches of allergen-specific immunotherapy and biological immune modifiers and also highlights the possibility of combining these two strategies to harness the advantages of both types of therapy and address current unmet clinical needs associated with these conditions.
Abstract - | Full Text - Therapies for allergic inflammation: refining strategies to induce tolerance | PDF (2,225 KB) - Therapies for allergic inflammation: refining strategies to induce tolerance
Articles
Focus on Asthma
Interleukin-25 induces type 2 cytokine production in a steroid-resistant interleukin-17RB+ myeloid population that exacerbates asthmatic pathology
Bryan C Petersen, Alison L Budelsky, Alan P Baptist, Matthew A Schaller & Nicholas W Lukacs
Published online: 29 April 2012 | doi:10.1038/nm.2735
Focus on Asthma
Commensal bacteria–derived signals regulate basophil hematopoiesis and allergic inflammation
David A Hill, Mark C Siracusa, Michael C Abt, Brian S Kim, Dmytro Kobuley, Masato Kubo, Taku Kambayashi, David F LaRosa, Ellen D Renner, Jordan S Orange, Frederic D Bushman & David Artis
Nature Medicine : 18, 538–546 (2012) | doi:10.1038/nm.2657
Focus on Asthma
IL-17A produced by αβ T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction
Makoto Kudo, Andrew C Melton, Chun Chen, Mary B Engler, Katherine E Huang, Xin Ren, Yanli Wang, Xin Bernstein, John T Li, Kamran Atabai, Xiaozhu Huang & Dean Sheppard
Nature Medicine: 18, 547–554 (2012) | doi:10.1038/nm.2684
Focus on Asthma
The tumor necrosis factor family member LIGHT is a target for asthmatic airway remodeling
Taylor A Doherty, Pejman Soroosh, Naseem Khorram, Satoshi Fukuyama, Peter Rosenthal, Jae Youn Cho, Paula S Norris, Heonsik Choi, Stefanie Scheu, Klaus Pfeffer, Bruce L Zuraw, Carl F Ware, David H Broide & Michael Croft
Nature Medicine: 17, 596–603 (2011) | doi:10.1038/nm.2356
Focus on Asthma
Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction
Deepak A Deshpande, Wayne C H Wang, Elizabeth L McIlmoyle, Kathryn S Robinett, Rachel M Schillinger, Steven S An, James S K Sham & Stephen B Liggett
Nature Medicine: 16, 1299–1304 (2010) | doi:10.1038/nm.2237
Focus on Asthma
CX3CR1 is required for airway inflammation by promoting T helper cell survival and maintenance in inflamed lung
Cyrille Mionnet, Vanessa Buatois, Akira Kanda, Valerie Milcent, Sebastien Fleury, David Lair, Marie Langelot, Yannick Lacoeuille, Edith Hessel, Robert Coffman, Antoine Magnan, David Dombrowicz, Nicolas Glaichenhaus & Valerie Julia
Nature Medicine: 16, 1305–1312 (2010) | doi:10.1038/nm.2253