Nobuaki Miyahara
Okayama University, Japan
Title: Importance of IL-23 to the development of emphysema
Biography
Biography: Nobuaki Miyahara
Abstract
Pulmonary emphysema is characterized by alveolar destruction and persistent inflammation of the airways. We have recently reported that IL-17A and Th17 cells play a critical role to the development of porcine pancreatic elastase (PPE)-induced emphysema. Differentiation of Th17 cells is shown to be induced by IL-23. To determine the contribution of IL-23 to the development of pulmonary emphysema a mouse model of PPE-induced emphysema was used in which responses of IL-23p19-deficient (IL-23-/-) and wild type (WT) mice were compared. Intra-tracheal instillation of PPE induced emphysematous changes in the lungs and was associated with increased levels of IL-23 in lung homogenates. Compared to WT mice, IL-23-/- mice developed significantly lower static compliance values and markedly reduced emphysematous changes on histological analyses following PPE-instillation. These changes were associated with lower levels of IL-17A and fewer Th17 cells in the lung. The neutrophilia seen in bronchoalveolar lavage (BAL) fluid of WT mice was attenuated in IL-23-/- mice, and the reduction was associated with decreased levels of KC and MIP-2 in BAL fluid. Treatment with anti-IL-23p40 monoclonal antibody significantly attenuated PPE-induced emphysematous changes in the lungs of WT mice. These data identify the important contributions of IL-23 to the development of elastase-induced pulmonary inflammation and emphysema, mediated through an IL-23-IL-17 pathway. Targeting IL-23 in emphysema may be a potential therapeutic strategy for delaying disease progression.