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

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

Ross, Rosie¹  Yá³  Crompton, Tessa³  Furmanski, Anna L.⁴  nez, Diana C.⁴ 

[1] and;and..Immunobiology Section, UCL Great Ormond Street Institute of Child Health, London, UK;Immunobiology Section, UCL Great Ormond Street Institute of Child Health, London, UK;School of Life Sciences, University of Bedfordshire, Luton, UK

关键词: allergy;    morphogen;    Gli1;    Sonic Hedgehog;    epithelia;   

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

CC BY