Protease Activated Receptor 4 as a Novel Modulator of Regulatory T Cell Function

Article


Peng, Q., Ratnasothy, K., Boardman, D. A., Jacob, J., Tung, S. T., McCluskey, D., Smyth, L., Lechler, R. I., Dorling, A. and Lombardi, G. 2019. Protease Activated Receptor 4 as a Novel Modulator of Regulatory T Cell Function. Frontiers in Immunology. 10 (Art. 1311).
AuthorsPeng, Q., Ratnasothy, K., Boardman, D. A., Jacob, J., Tung, S. T., McCluskey, D., Smyth, L., Lechler, R. I., Dorling, A. and Lombardi, G.
Abstract

Regulatory T cells (Tregs) are a subpopulation of T cells that maintain immunological tolerance. In inflammatory responses the function of Tregs is tightly controlled by several factors including signaling through innate receptors such as Toll like receptors and anaphylatoxin receptors allowing an effective immune response to be generated. Protease-activated receptors (PARs) are another family of innate receptors expressed on multiple cell types and involved in the pathogenesis of autoimmune disorders. Whether proteases are able to directly modulate Treg function is unknown. Here, we show using two complimentary approaches that signaling through PAR-4 influences the expression of CD25, CD62L and CD73, the suppressive capacity, and the stability of Tregs, via phosphorylation of FoxO1 and negative regulation of PTEN and FoxP3. Taken together, our results demonstrate an important role of PAR4 in tuning the function of Tregs and open the possibility of targeting PAR4 to modulate immune responses.

JournalFrontiers in Immunology
Journal citation10 (Art. 1311)
ISSN1664-3224
Year2019
PublisherFrontiers Media
Publisher's version
License
File Access Level
Anyone
Digital Object Identifier (DOI)doi:10.3389/fimmu.2019.01311
Web address (URL)https://doi.org/10.3389/fimmu.2019.01311
Publication dates
Online18 Jun 2019
Publication process dates
Accepted23 May 2019
Deposited18 Jun 2019
FunderBritish Heart Foundation (BHF)
Copyright holder© 2019 The Authors.
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