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Harnessing proteases for T regulatory cell immunotherapy

Lookup NU author(s): Dr Shoba AmarnathORCiD, Marnie BrownORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2020 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. The immune system is tightly regulated by a subset of T cells defined as regulatory T cells (Tregs). Tregs maintain immune homeostasis by restraining unwarranted immune cell activation and effector function. Here, we discuss an important but underappreciated role of proteases in controlling Treg function. Proteases regulate a number of vital processes that determine T cell immune responses and some of them such as furin, ADAM (through regulating LAG receptor), MALT, and asparaginyl endopeptidase are implicated in Treg immunobiology. Targeted protease inhibition, using either small molecule inhibitors or gene deficient mice has demonstrated their specificity in modulating Treg function in experimental murine models. These data further highlight the ability of proteases to specifically regulate Tregs but no other T effector lineages. Taken together, it is apparent that incorporating proteases as targets within Treg cell engineering protocols may enable generation of robust Treg cellular therapeutics. These engineered Tregs may possess enhanced regulatory function along with resistance to lineage deviation in inflammatory disease such as colitis and graft versus host disease. Within this review, we summarize research on the role of proteases in regulating Treg function and discuss the translational potential of harnessing Treg function by targeting protease driven regulatory pathways.

Publication metadata

Author(s): Amarnath S, Brown ML

Publication type: Review

Publication status: Published

Journal: European Journal of Immunology

Year: 2020

Volume: 50

Issue: 6

Pages: 770-778

Print publication date: 01/06/2020

Online publication date: 08/05/2020

Acceptance date: 06/05/2020

ISSN (print): 0014-2980

ISSN (electronic): 1521-4141

Publisher: Wiley-VCH Verlag


DOI: 10.1002/eji.201948270

PubMed id: 32383480