| First Author | Kirstein F | Year | 2016 |
| Journal | J Allergy Clin Immunol | Volume | 137 |
| Issue | 6 | Pages | 1852-1862.e9 |
| PubMed ID | 26688514 | Mgi Jnum | J:314809 |
| Mgi Id | MGI:6822789 | Doi | 10.1016/j.jaci.2015.10.036 |
| Citation | Kirstein F, et al. (2016) Role of IL-4 receptor alpha-positive CD4(+) T cells in chronic airway hyperresponsiveness. J Allergy Clin Immunol 137(6):1852-1862.e9 |
| abstractText | BACKGROUND: TH2 cells and their cytokines are associated with allergic asthma in human subjects and with mouse models of allergic airway disease. IL-4 signaling through the IL-4 receptor alpha (IL-4Ralpha) chain on CD4(+) T cells leads to TH2 cell differentiation in vitro, implying that IL-4Ralpha-responsive CD4(+) T cells are critical for the induction of allergic asthma. However, mechanisms regulating acute and chronic allergen-specific TH2 responses in vivo remain incompletely understood. OBJECTIVE: This study defines the requirements for IL-4Ralpha-responsive CD4(+) T cells and the IL-4Ralpha ligands IL-4 and IL-13 in the development of allergen-specific TH2 responses during the onset and chronic phase of experimental allergic airway disease. METHODS: Development of acute and chronic ovalbumin (OVA)-induced allergic asthma was assessed weekly in CD4(+) T cell-specific IL-4Ralpha-deficient BALB/c mice (Lck(cre)IL-4Ralpha(-/lox)) and respective control mice in the presence or absence of IL-4 or IL-13. RESULTS: During acute allergic airway disease, IL-4 deficiency did not prevent the onset of TH2 immune responses and OVA-induced airway hyperresponsiveness or goblet cell hyperplasia, irrespective of the presence or absence of IL-4Ralpha-responsive CD4(+) T cells. In contrast, deficiency of IL-13 prevented allergic asthma, irrespective of the presence or absence of IL-4Ralpha-responsive CD4(+) T cells. Importantly, chronic allergic inflammation and airway hyperresponsiveness were dependent on IL-4Ralpha-responsive CD4(+) T cells. Deficiency in IL-4Ralpha-responsive CD4(+) T cells resulted in increased numbers of IL-17-producing T cells and, consequently, increased airway neutrophilia. CONCLUSION: IL-4-responsive T helper cells are dispensable for acute OVA-induced airway disease but crucial in maintaining chronic asthmatic pathology. |
