Journal of leukocyte biology

Frontline Science: Shh production and Gli signaling is activated in vivo in lung, enhancing the Th2 response during a murine model of allergic asthma.

PMID 28235772


The pathophysiology of allergic asthma is driven by Th2 immune responses after aeroallergen inhalation. The mechanisms that initiate, potentiate, and regulate airway allergy are incompletely characterized. We have shown that Hh signaling to T cells, via downstream Gli transcription factors, enhances T cell conversion to a Th2 phenotype. In this study, we showed for the first time, to our knowledge, that Gli-dependent transcription is activated in T cells in vivo during murine AAD, a model for the immunopathology of asthma, and that genetic repression of Gli signaling in T cells decreases the differentiation and recruitment of Th2 cells to the lung. T cells were not the only cells that expressed activated Gli during AAD. A substantial proportion of eosinophils and lung epithelial cells, both central mediators of the immunopathology of asthma, also underwent Hh/Gli signaling. Finally, Shh increased Il-4 expression in eosinophils. We therefore propose that Hh signaling during AAD is complex, involving multiple cell types, signaling in an auto- or paracrine fashion. Improved understanding of the role of this major morphogenetic pathway in asthma may give rise to new drug targets for this chronic condition.