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The emerging role of ECM crosslinking in T cell mobility as a hallmark of immunosenescence in humans

Moreau, Jean-Francois and Pradeu, Thomas and Grignolio, Andrea and Nardini, Christine and Castiglione, Filippo and Tieri, Paolo and Capri, Miriam and Salvioli, Stefano and Taupin, Jean-Luc and Garagnani, Paolo and Franceschi, Claudio (2017) The emerging role of ECM crosslinking in T cell mobility as a hallmark of immunosenescence in humans. Ageing Research Reviews, 35. pp. 322-335. ISSN 15681637


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Immunosenescence is thought to result from cellular aging and to reflect exposure to environmental stressors and antigens, including cytomegalovirus (CMV). However, not all of the features of immunosenescence are consistent with this view, and this has led to the emergence of the sister theory of “inflammaging”. The recently discovered diffuse tissue distribution of resident memory T cells (TRM) which don't recirculate, calls these theories into question. These cells account for most T cells residing in barrier epithelia which sit in and travel through the extracellular matrix (ECM). With almost all studies to date carried out on peripheral blood, the age-related changes of the ECM and their consequences for T cell mobility, which is crucial for the function of these cells, have been largely ignored. We propose an update of the theoretical framework of immunosenescence, based on a novel hypothesis: the increasing stiffness and cross-linking of the senescent ECM lead to a progressive immunodeficiency due to an age-related decrease in T cell mobility and eventually the death of these cells. A key element of this mechanism is the mechanical stress to which the cell cytoplasm and nucleus are subjected during passage through the ECM. This hypothesis is based on an “evo-devo” perspective bringing together some major characteristics of aging, to create a single interpretive framework for immunosenescence.

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Item Type: Published Article or Volume
Moreau, Jean-Francois
Pradeu, Thomas
Grignolio, Andrea
Nardini, Christine
Castiglione, Filippo
Tieri, Paolo
Capri, Miriam
Salvioli, Stefano
Taupin, Jean-Luc
Garagnani, Paolo
Franceschi, Claudio
Depositing User: Thomas Pradeu
Date Deposited: 18 Oct 2020 02:39
Last Modified: 18 Oct 2020 02:39
Item ID: 18251
Journal or Publication Title: Ageing Research Reviews
Official URL:
DOI or Unique Handle: 10.1016/j.arr.2016.11.005
Date: 2017
Page Range: pp. 322-335
Volume: 35
ISSN: 15681637

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