title: The emerging role of ECM crosslinking in T cell mobility as a hallmark of immunosenescence in humans.
abstract: 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.
authors.affiliation: University of Bordeaux, CNRS-UMR5164, 146 rue Léo Saignat, 33076 Bordeaux, France; CHU Bordeaux, Place Amélie Raba-Léon, Bordeaux, France. Electronic address: jfmoreau@u-bordeaux.fr.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Moreau
authors.affiliation: University of Bordeaux, CNRS-UMR5164, 146 rue Léo Saignat, 33076 Bordeaux, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pradeu
authors.affiliation: University of Rome "La Sapienza", Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Grignolio
authors.affiliation: Personalgenomics, Strada le Grazie, Verona, Italy.
authors.forename: Christine
authors.initials: C
authors.lastname: Nardini
authors.affiliation: Consiglio Nazionale delle Ricerche, Istituto per le Applicazioni del Calcolo, Rome, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Castiglione
authors.affiliation: Consiglio Nazionale delle Ricerche, Istituto per le Applicazioni del Calcolo, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Tieri
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Interdepartmental Centre "L.Galvani" for Bioinformatics, Biophysics and Biocomplexity, Via San Giacomo, 12, University of Bologna, 40126 Bologna, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Capri
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Interdepartmental Centre "L.Galvani" for Bioinformatics, Biophysics and Biocomplexity, Via San Giacomo, 12, University of Bologna, 40126 Bologna, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Salvioli
authors.affiliation: Université Paris-Diderot, INSERM U1160, Paris, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Taupin
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Interdepartmental Centre "L.Galvani" for Bioinformatics, Biophysics and Biocomplexity, Via San Giacomo, 12, University of Bologna, 40126 Bologna, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Garagnani
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Interdepartmental Centre "L.Galvani" for Bioinformatics, Biophysics and Biocomplexity, Via San Giacomo, 12, University of Bologna, 40126 Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
mesh_terms: D000375:Aging / Q000276:immunology*; D002465:Cell Movement / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology*; D006801:Humans; D000068884:Immunosenescence / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology
keywords: Aging; Extracellular matrix; Immune cells; Immunosenescence; Mobility