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Exploring the role of mechanical cues in T cell function

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Title Exploring the role of mechanical cues in T cell function
 
Creator Liu, Chinky Shiu Chen
 
Subject Cancer Biology and Inflammatory Disorder Division
 
Description T lymphocytes are constantly subjected to mechanical cues from their microenvironment. The
past few decades have seen a significant development in scientific research concerning the
crucial role of biophysical forces in governing various T lymphocyte-mediated processes.
Mounting research have confirmed that T lymphocyte activation is critically dependent on its
capacity to sense and respond to mechanical forces which are generated during its interaction
with cellular partners and with its microenvironment. Despite extensive research on the role
of mechanical forces on T lymphocyte biology, no dedicated T lymphocyte-intrinsic
mechanosensory module was identified until recently. In the following thesis, I have
described the role of Piezo1 mechanosensors in T lymphocyte function, particularly in the
contexts of T lymphocyte activation and migration. Upon interaction with cognate antigen
presenting cells (APCs), T lymphocytes experience significant mechanical force which
activates Piezo1 channels. Activated Piezo1 allows influx of extracellular calcium which
triggers calpain-dependent polymerisation and remodelling of the actin cytoskeletal scaffold.
This event is crucial for formation and stabilisation of the T cell-APC immunological synapse,
thereby facilitating optimal T lymphocyte activation. Moreover, Piezo1-mediated
mechanotransduction also plays a critical role in T lymphocyte chemotactic migration.
Downregulation of Piezo1 resulted in dramatically impaired motility of T lymphocytes in
response to stimulus. Thus, we have identified a previously unknown pathway of Piezo1-
mediated mechanoregulation of T lymphocyte function.
 
Date 2020
 
Type Thesis
NonPeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2837/1/Chinky_Shiu_Chen_Liu_Thesis.pdf
Liu, Chinky Shiu Chen (2020) Exploring the role of mechanical cues in T cell function. PhD thesis, JADAVPUR UNIVERSITY.
 
Relation http://www.eprints.iicb.res.in/2837/