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

Jean Francois Moreau, Thomas Pradeu, Andrea Grignolio, Christine Nardini, Filippo Castiglione, Paolo Tieri, Miriam Capri, Stefano Salvioli, Jean Luc Taupin, Paolo Garagnani, Claudio Franceschi

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
JournalAgeing Research Reviews
Publication statusAccepted/In press - Jun 1 2016


  • Aging
  • Extracellular matrix
  • Immune cells
  • Immunosenescence
  • Mobility

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Ageing
  • Molecular Biology
  • Neurology


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