Modeling T<inf>H</inf>2 responses and airway inflammation to understand fundamental mechanisms regulating the pathogenesis of asthma

Foster, Paul S.; Maltby, Steven; Mattes, Joerg; Rosenberg, Helene F.; Tay, Hock L.; Hogan, Simon P.; Collison, Adam M.; Yang, Ming; Kaiko, Gerard E.; Hansbro, Philip M.; Kumar, Rakesh K.

Title: Modeling TH2 responses and airway inflammation to understand fundamental mechanisms regulating the pathogenesis of asthma
Creator: Foster, Paul S.; Maltby, Steven; Mattes, Joerg; Rosenberg, Helene F.; Tay, Hock L.; Hogan, Simon P.; Collison, Adam M.; Yang, Ming; Kaiko, Gerard E.; Hansbro, Philip M.; Kumar, Rakesh K.
Relation: Immunological Reviews Vol. 278, Issue 1, p. 20-40
Publisher Link: http://dx.doi.org/10.1111/imr.12549
Publisher: Wiley-Blackwell
Resource Type: journal article
Date: 2017
Description: In this review, we highlight experiments conducted in our laboratories that have elucidated functional roles for CD4⁺ T-helper type-2 lymphocytes (T_H2 cells), their associated cytokines, and eosinophils in the regulation of hallmark features of allergic asthma. Notably, we consider the complexity of type-2 responses and studies that have explored integrated signaling among classical T_H2 cytokines (IL-4, IL-5, and IL-13), which together with CCL11 (eotaxin-1) regulate critical aspects of eosinophil recruitment, allergic inflammation, and airway hyper-responsiveness (AHR). Among our most important findings, we have provided evidence that the initiation of T_H2 responses is regulated by airway epithelial cell-derived factors, including TRAIL and MID1, which promote T_H2 cell development via STAT6-dependent pathways. Further, we highlight studies demonstrating that microRNAs are key regulators of allergic inflammation and potential targets for anti-inflammatory therapy. On the background of T_H2 inflammation, we have demonstrated that innate immune cells (notably, airway macrophages) play essential roles in the generation of steroid-resistant inflammation and AHR secondary to allergen- and pathogen-induced exacerbations. Our work clearly indicates that understanding the diversity and spatiotemporal role of the inflammatory response and its interactions with resident airway cells is critical to advancing knowledge on asthma pathogenesis and the development of new therapeutic approaches.
Subject: allergic inflammation; cytokine; innate immunity; microRNA; steroid resistance; T-helper cell
Identifier: http://hdl.handle.net/1959.13/1390570
Identifier: uon:33088
Identifier: ISSN:0105-2896
Language: eng
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Modeling TH2 responses and airway inflammation to understand fundamental mechanisms regulating the pathogenesis of asthma