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Modeling T H 2 responses and airway inflammation to understand fundamental mechanisms regulating the pathogenesis of asthma
Author(s) -
Foster Paul S.,
Maltby Steven,
Rosenberg Helene F.,
Tay Hock L.,
Hogan Simon P.,
Collison Adam M.,
Yang Ming,
Kaiko Gerard E.,
Hansbro Philip M.,
Kumar Rakesh K.,
Mattes Joerg
Publication year - 2017
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12549
Subject(s) - immunology , inflammation , pathogenesis , eosinophil , immune system , eotaxin , allergic inflammation , biology , t cell , asthma , medicine
Summary In this review, we highlight experiments conducted in our laboratories that have elucidated functional roles for CD 4 + T‐helper type‐2 lymphocytes ( T H 2 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 H 2 cytokines ( IL ‐4, IL ‐5, and IL ‐13), which together with CCL 11 (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 H 2 responses is regulated by airway epithelial cell‐derived factors, including TRAIL and MID 1, which promote T H 2 cell development via STAT 6‐dependent pathways. Further, we highlight studies demonstrating that micro RNAs are key regulators of allergic inflammation and potential targets for anti‐inflammatory therapy. On the background of T H 2 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.