Recent advances in understanding the cellular and molecular mechanisms of atopy have shed light on potential targets for the development of new therapies for allergic diseases. In this issue of the JCI, Seshasayee et al. provide direct in vivo evidence that OX40 has critical roles in allergic inflammation mediated by thymic stromal lymphopoietin (TSLP) (see the related article beginning on page 3868). Blockade of interactions between OX40 on Th2 cells and OX40 ligand (OX40L) on TSLP-activated DCs using an OX40L-specific monoclonal antibody, inhibited Th2 cell-mediated immune responses in both mouse and nonhuman primate models of allergic inflammation. The results point to potential therapeutic approaches to targeting the cellular and molecular mechanism underlying TSLP-mediated allergic inflammation.