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Int J Biochem Cell Biol. 2017 Nov;92:95-103. doi: 10.1016/j.biocel.2017.09.015. Epub 2017 Sep 22.

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

Author information

1
Department of Veterinary Biosciences, Melbourne Veterinary School, University of Melbourne, Parkville, VIC 3010, Australia.
2
Department of Biochemistry & Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
3
Department of Veterinary Biosciences, Melbourne Veterinary School, University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: cpagel@unimelb.edu.au.

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.

KEYWORDS:

Cell differentiation; Cell surface molecules; Knockout mice; Protease-activated receptors; T cells; Thymus

PMID:
28951199
DOI:
10.1016/j.biocel.2017.09.015
[Indexed for MEDLINE]

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