Blocking IL-25 prevents airway hyperresponsiveness in allergic asthma

Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
The Journal of allergy and clinical immunology (Impact Factor: 11.25). 01/2008; 120(6):1324-31. DOI: 10.1016/j.jaci.2007.07.051
Source: PubMed

ABSTRACT IL-25 (IL-17E), a member of the IL-17 family of immunoregulatory cytokines, has been implicated in the regulation of type 2 immunity. Its roles in antigen-driven airway inflammation and airway hyperresponsiveness (AHR) remain to be fully established.
We sought to determine whether a neutralizing antibody against IL-25 represents a novel therapeutic for airway inflammation and hyperresponsiveness.
We generated a neutralizing mAb against IL-25 and used this to inhibit IL-25 in a mouse model of allergic airway disease.
Blocking IL-25 in an experimental model of allergic asthma prevented AHR, a critical feature of clinical asthma. Administration of anti-IL-25 mAb during the sensitization phase resulted in significantly reduced levels of IL-5 and IL-13 production, eosinophil infiltration, goblet cell hyperplasia, and serum IgE secretion, and prevented AHR. Even more striking was the ability of anti-IL-25 mAb, administered only during the challenge phase of the response, specifically to prevent AHR even during an ongoing type 2 inflammatory response in the lungs.
IL-25 is critical for development of AHR.
We define a novel pathway for the induction of AHR and suggest that IL-25 represents an important therapeutic target for the treatment of asthma. Significantly, our antibody also blocks the binding of human IL-25 to its receptor.

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Available from: See Heng Wong, Aug 22, 2015
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    • "February 2012 | Volume 2 | Article 10 | 1 hyper-responsiveness (Wills-Karp et al., 1998). Recently, other subsets of T-helper cells have been linked to asthma pathogenesis , including Th9 (Shimbara et al., 2000; Erpenbeck et al., 2003), Th25 (Tamachi et al., 2006; Ballantyne et al., 2007), and Th22 cells (Nakagome et al., 2011). A subset of lung-infiltrating T-cells known as Th17 cells has been described to account for neutrophilic airway inflammation, but also for enhanced Th2-cell-mediated eosinophilic airway inflammation (Wakashin et al., 2008). "
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