Environmental and genetic contribution in airway epithelial barrier in asthma pathogenesis.
OBJECTIVE
To examine the recent, most relevant genetic and epigenetic modifications of the epithelial barrier in response to the environmental factors, including allergens, viruses, and pollutants, susceptible to participate to asthma.


RESULTS
IL-33 and TSLP gene polymorphisms are found in almost all asthma studies. Recent data have highlighted a new population of innate lymphoid cells, activated by these two cytokines, and mediating type 2 innate immunity dependent asthma. Gene variants of innate pattern recognition receptors associated with asthma have been evidenced in early viral infected high-risk birth cohorts, as well as polymorphisms in pathways involved in type I interferon (IFN) production, giving further insight into the role of viruses in asthma development. Novel epigenetic mechanisms have been evidenced in asthma and in response to the environmental pollutants, and point out genes like TSLP, which may link environmental pollution and asthma.


CONCLUSIONS
Genetic data support the role of a specific set of epithelial-derived proTh2 cytokines, including IL-33 and TSLP, as well as the role of decreased type I IFN in virus-induced impaired epithelial barrier. Epigenetic modifications of epithelial genes are promising mechanisms that warrant further investigation.
Pulmonary Immunity, Institut National de la Santé Et de la Recherche Médicale, U1019, Institut Pasteur de Lille, Lille, France. anne.tsicopoulos@pasteur-lille.fr
Anne
A
Tsicopoulos
Patricia
P
de Nadai
Corine
C
Glineur
D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000235:genetics*; D016207:Cytokines / Q000235:genetics*; D004781:Environmental Exposure / Q000009:adverse effects; D044127:Epigenesis, Genetic; D059647:Gene-Environment Interaction; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007370:Interferon Type I / Q000276:immunology; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics*; D011110:Polymorphism, Genetic; D051192:Receptors, Pattern Recognition / Q000235:genetics*; D020545:Respiratory Mucosa / Q000276:immunology*; D058408:Th1-Th2 Balance; D000094632:Thymic Stromal Lymphopoietin
D000485:Allergens; D016207:Cytokines; C506536:IL33 protein, human; D007370:Interferon Type I; D000067596:Interleukin-33; D007378:Interleukins; D051192:Receptors, Pattern Recognition; D000094632:Thymic Stromal Lymphopoietin