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

Nidhish Francis, Allison Every, Babatunde Ayodele, Rob Pike, Eleanor Mackie, Charles Pagel

Research output: Contribution to journalArticle

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Abstract

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.
Original languageEnglish
Pages (from-to)95-103
Number of pages9
JournalInternational Journal of Biochemistry and Cell Biology
Volume92
Early online dateSep 2017
DOIs
Publication statusPublished - 09 Nov 2017

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PAR-2 Receptor
T-cells
Lymphocytes
T-Lymphocytes
Thymus
Periodontitis
Thymus Gland
Propidium
Annexin A5
Thymocytes

Cite this

Francis, Nidhish ; Every, Allison ; Ayodele, Babatunde ; Pike, Rob ; Mackie, Eleanor ; Pagel, Charles. / A T cell-specific knockout reveals an important role for protease-activated receptor 2 in lymphocyte development. In: International Journal of Biochemistry and Cell Biology. 2017 ; Vol. 92. pp. 95-103.
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A T cell-specific knockout reveals an important role for protease-activated receptor 2 in lymphocyte development. / Francis, Nidhish; Every, Allison; Ayodele, Babatunde; Pike, Rob; Mackie, Eleanor; Pagel, Charles.

In: International Journal of Biochemistry and Cell Biology, Vol. 92, 09.11.2017, p. 95-103.

Research output: Contribution to journalArticle

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AU - Every, Allison

AU - Ayodele, Babatunde

AU - Pike, Rob

AU - Mackie, Eleanor

AU - Pagel, Charles

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