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

作者:Francis Nidhish; Every Alison L; Ayodele Babatunde A; Pike Robert N; Mackie Eleanor J; Pagel Charles N*
来源:International Journal of Biochemistry & Cell Biology, 2017, 92: 95-103.
DOI:10.1016/j.biocel.2017.09.015

摘要

Activation of protease-activated receptor-2 (PAR(2)) expressed by T cells has been linked to the bone loss associated with periodontitis. We generated PAR(2) conditional-null mice and crossed these with mice expressing Cre recombinase under control of the Lck proximal promoter, to produce T cell-specific PAR(2)-null mice in order to further study the cellular mechanism involved in periodontitis. Here we report that efficient deletion of PAR(2) in thymocytes isolated from T cell-specific PAR(2)-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 PAR(2) 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 PAR(2)-null mice. No change in the proportion of Ki67 positive cells was observed in sections of thymus from T cell specific PAR(2)-null mice, suggesting that the depletion of T cell sub-populations in T cell-specific PAR(2)-null mice resulted from increased apoptosis rather than reduced proliferation. Together, these results demonstrate that PAR(2) plays an important and previously unrecognised anti-apoptotic role in T cell development and suggest that the PAR(2) conditional-null mouse will be an important resource for determining tissue and cell specific effects of PAR(2).

  • 出版日期2017-11