Thus, the difference in outcomes between Smo inhibition in models of allergic disease in lung and skin would appear to be the result of the different effects of lowering Shh expression in the two tissues: in lung, Shh signals to T-cells to promote Th2 differentiation and function driving allergic asthma, so that reduction in its expression ameliorates allergic disease, whereas in skin Shh signals to induce regulatory T-cell function and so its upregulation is protective against inflammation and disease, and Smo inhibition aggravates it (4, 5, 15). The gene discussed is SHH; the disease is allergic asthma.