Neuroserpin regulates human T cell-T cell interactions and proliferation through inhibition of tissue plasminogen activator.

Autor: Loef EJ; School of Biological Sciences, The University of Auckland, Auckland, New Zealand.; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand., Brooks AES; School of Biological Sciences, The University of Auckland, Auckland, New Zealand.; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand., Lorenz N; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand.; School of Medical Sciences, The University of Auckland, Auckland, New Zealand., Birch NP; School of Biological Sciences, The University of Auckland, Auckland, New Zealand.; Centre for Brain Research and Brain Research New Zealand, The University of Auckland, Auckland, New Zealand., Dunbar PR; School of Biological Sciences, The University of Auckland, Auckland, New Zealand.; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand.
Jazyk: angličtina
Zdroj: Journal of leukocyte biology [J Leukoc Biol] 2020 Jan; Vol. 107 (1), pp. 145-158. Date of Electronic Publication: 2019 Oct 31.
DOI: 10.1002/JLB.2A1019-098RR
Abstrakt: T cells play a key role in mounting an adaptive immune response. T cells are activated upon recognition of cognate Ag presented by an APC. Subsequently, T cells adhere to other activated T cells to form activation clusters, which lead to directed secretion of cytokines between communicating cells. T cell activation clusters have been implicated in regulating activation, proliferation, and memory formation in T cells. We previously reported the expression of the protease inhibitor neuroserpin by human T cells and showed that expression and intracellular localization is regulated following T cell activation. To gain a better understanding of neuroserpin in the proteolytic environment postactivation we assessed its role in human T cell clustering and proliferation. Neuroserpin knockdown increased T cell proliferation and cluster formation following T cell activation. This increased cluster formation was dependent on the proteases tissue plasminogen activator (tPA) and plasmin. Furthermore, neuroserpin knockdown or plasmin treatment of T cells increased the cleavage of annexin A2, a known plasmin target that regulates the actin cytoskeleton. Live cell imaging of activated T cells further indicated a role of the actin cytoskeleton in T cell clustering. The inhibition of actin regulators myosin ATPase and Rho-associated protein kinase signaling completely reversed the neuroserpin knockdown-induced effects. The results presented in this study reveal a novel role for neuroserpin and the proteolytic environment in the regulation of T cell activation biology.
(©2019 Society for Leukocyte Biology.)
Databáze: MEDLINE
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