Neuroimmune semaphorin 4A downregulates the severity of allergic response

To define the role of Sema4A in allergic response, we employed Sema4A(−/−) and WT mice in the experimental model of OVA-induced allergic airway inflammation. We observed a selective increase in eosinophilic airway infiltration accompanied by bronchial epithelial cell hyperplasia in allergen-treated Sema4A(−/−) mice relative to WT mice. This enhanced inflammatory response was associated with a selective increase in BAL IL-13 content, augmented airway hyperreactivity, and lower Treg numbers. In vivo allergen-primed Sema4A(−/−) CD4+ T cells were more effective in transferring Th2 response to naïve mice as compared to WT CD4+ T cells. T cell proliferation and IL-13 productions in OVA(323–339) - restimulated Sema4A(−/−) cell cultures were upregulated. Generated bone marrow chimeras showed an equal importance of both lung resident cell and inflammatory cell Sema4A expression in optimal disease regulation. These data provide a new insight into Sema4A biology and define Sema4A as an important regulator of Th2-driven lung pathophysiology.