Pulmonary Epithelial Cell-Derived Cytokine TGF-b1 is a Critical Cofactor for Enhanced Innate Lymphoid Cell Function

L. Denney, A.J. Byrne, et al.

Immunity 43, 945-958 (2015)

Speaker: Cheng, Chia-Ying (鄭嘉瑩)                           Time: 13:10~14:00, Jun. 01, 2016

Commentator: Dr. Hsu, Yu-Hsiang (許育祥 教授)     Place: Room 601

Abstract:

Innate lymphoid cells (ILCs) have an important role in mouse models of infection, inflammation and tissue repair.  ILC group 2 (ILC2) represents a critical source of type 2 cytokines including IL-5, IL-9 and IL-13.  In allergic asthma, pulmonary epithelial cell-derived IL-33 plays an important role in inducing ILC2 and type2 immune response.  Previous studies showed that transforming growth factor beta (TGF-β) enhanced the development of airway remodeling in allergic asthma.  However, the mechanism of epithelial-derived TGF-b1effects the ILC2 or the type 2 immune response in allergic asthma had not yet been addressed.  The authors hypothesized that the epithelial-derived TGF-b1 modulated the immune response through the IL-33-induced ILC2 immune response.  To investigate the specific role of epithelial-derived TGF-b1 in the pulmonary immune response to inhaled allergen, the authors generated mice with a conditional deletion of Tgfb1 in epithelial cell.  First, they found epithelial specific deletion of TGF-b greatly diminished the house dust mite (HDM)-induced type 2 immune response and the accumulation of ILC2 in pulmonary epithelium.  Second, they found the IL-33-induced ILC2 population and type 2 inflammation was decreased in epithelium specific Tgfb1 deletion mice.  Third, epithelial specific deletion of TGF-b1 enhanced the GATA-3-supressive transcription factor Sox4 (sex determining region Y, box4) in lung tissue.  Moreover, TGF-b1 induced chemoactivity of ILC2 migration to local site in normal pulmonary epithelium.  In conclusion, the epithelial-derived TGF-b is a crucial driver of the early allergic immune response to inhaled stimuli through enhancing IL-33-induced ILC2 immune response in the lung.  This research highlights the central role of local environmental niche in defining the nature and the magnitude of immune responses.

Reference：

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