A T cell-specific knockout reveals an important role for protease-activated receptor 2 in lymphocyte development

Activation of protease-activated receptor-2 (PAR₂) expressed by T cells has been linked to the bone loss associated with periodontitis. We generated PAR₂ conditional-null mice and crossed these with mice expressing Cre recombinase under control of the Lck proximal promoter, to produce T cell-specific PAR₂-null mice in order to further study the cellular mechanism involved in periodontitis. Here we report that efficient deletion of PAR₂ in thymocytes isolated from T cell-specific PAR₂-null mice resulted in thymic and splenic hypoplasia and a reduction in the cells of the cortex and a loss of distinction between the cortex and the medulla of the thymus. FACS analysis confirmed significant reductions in CD4 and CD8 double negative (DN3 and DN4) sub-populations, as well as double positive and single positive T cells, in T cell-specific PAR₂-null mice compared to Cre expressing PAR₂ wild-type mice. The proportion of annexin V positive and propidium iodide negative cells was increased in CD4 and CD8 double negative, double positive and single positive T cells from T cell-specific PAR₂-null mice. No change in the proportion of Ki67 positive cells was observed in sections of thymus from T cell-specific PAR₂-null mice, suggesting that the depletion of T cell sub-populations in T cell-specific PAR₂-null mice resulted from increased apoptosis rather than reduced proliferation. Together, these results demonstrate that PAR₂ plays an important and previously unrecognised anti-apoptotic role in T cell development and suggest that the PAR₂ conditional-null mouse will be an important resource for determining tissue and cell specific effects of PAR₂.