Neuroimmune semaphorin 4D is necessary for optimal lung allergic inflammatory response (175.16)

Abstract Neuroimmune semaphorin 4D (Sema4D) was found to be expressed and function in the nervous and immune systems. In the immune system, Sema4D is constitutively expressed on T cells and regulates T cell priming. Currently available data suggest that Sema4D has crucial stimulatory functions in a broad range of cells including macrophages, DC, NK cells, and neutrophils. We hypothesized that Sema4D plays a critical non-redundant regulatory role in allergic airway response. To test our hypothesis, we employed Sema4D-/- and WT mice in the well-defined mouse model of OVA-induced experimental asthma. We observed a decrease in eosinophilic airway infiltration in allergen-treated Sema4D-/- mice relative to WT mice. This reduced allergic inflammatory response was associated with decreased BAL IL-5, IL-13, and TGFb1 levels. In addition, T cell proliferation in OVA323-339 - restimulated Sema4D-/- cell cultures were downregulated. However, airway hyperreactivity to methacholine challenges was not affected by Sema4D deficiency. These data provide a new insight into Sema4D biology and define Sema4D as an important regulator of Th2-driven lung pathophysiology.