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Full text release has been delayed at the author's request until January 19, 2027

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Piezo1: An Important Regulator of CD4+ T Cell Biology

Santin, Alicia Virginia
http://orcid.org/0000-0002-5638-0861
http://rave.ohiolink.edu/etdc/view?acc_num=case17259881746728

Abstract Details

2025, Doctor of Philosophy, Case Western Reserve University, Pathology.
Throughout their lives, T cells must navigate divergent hemodynamic environments to successfully respond to infection, injury, and stress. From the complex array of fluid dynamics found throughout the bloodstream, to the relatively static, matrix-defined parenchyma of tissues, T cells must effectively perceive and process their extracellular environment to make decisions about motility, growth, differentiation, and effector function. Understanding their environment is accomplished through an array of signaling cascades mediated by specialized proteins that are mechanosensing, including structural components of the cytoskeleton, adhesion molecules, and stretch-activated ion channels. To mount an appropriate immune response, naïve T cells must exit from the bloodstream and enter secondary lymphoid organs for antigen surveillance, recognize cognate antigen presented by antigen presenting cells, and effectively proliferate, differentiate, and fine tune its effector function. Effector T cells must then navigate back through the bloodstream to the site of inflammation. Notably, studies of the molecular mechanism of these processes have thus far largely neglected the important contribution of intrinsic mechanical forces. Because each of these processes is regulated, in part, by mechanosensation, the focus of the present work is to assess the role in T cell biology of a stretch-activated ion channel known to be highly expressed in T cells, Piezo1. We first generated and characterized a mouse model with a T cell specific deletion of Piezo1. This model afforded us the opportunity to assess the role of Piezo1 in vivo in all aspects of T cell biology leading us to demonstrate three insights. First, although Piezo1 decreased intrinsic T cell motility, Piezo1 is dispensable in naïve T cell homing at steady state and during inflammation. Second, Piezo1 restrains T cell overresponse and upregulation of inhibitory molecules upon TCR activation but is not necessary for successful T cell activation. Third, Piezo1 restrains inflammatory TH1 and TH17 differentiation yet is required for the induction of autoimmune mouse models of multiple sclerosis. Finally, Piezo1 depleted T cells are incapable of inducing phenotypic autoimmune diseases because Piezo1 maintains the persistence of effector CD4+ T cells, and without a continuous pool of newly activated CD4+ T cells, disease pathogenesis could not occur.
Alex Huang (Advisor)
Alan Levine (Committee Chair)
George Dubyak (Committee Member)
Wendy Goodman (Committee Member)
Tsan Xiao (Committee Member)
Clive Hamlin (Committee Member)
105 p.
Cellular Biology; Immunology; Pathology
T cell biology; mechanosensation; Piezo1; T cell migration; T cell activation; T cell differentiation; effector T cell; T cell persistence; autoimmunity; EAE; multiple sclerosis

Recommended Citations

Citations

  • Santin, A. V. (2025). Piezo1: An Important Regulator of CD4+ T Cell Biology [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case17259881746728

    APA Style (7th edition)

  • Santin, Alicia. Piezo1: An Important Regulator of CD4+ T Cell Biology. 2025. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case17259881746728.

    MLA Style (8th edition)

  • Santin, Alicia. "Piezo1: An Important Regulator of CD4+ T Cell Biology." Doctoral dissertation, Case Western Reserve University, 2025. http://rave.ohiolink.edu/etdc/view?acc_num=case17259881746728

    Chicago Manual of Style (17th edition)

case17259881746728
© 2025, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.