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

The emerging role of ECM crosslinking in T cell mobility as a hallmark of immunosenescence in humans. Ageing Res Rev. 2016 Nov 19;: Authors: Moreau JF, Pradeu T, GRignolio A, Nardini C, Castiglione F, Tieri P, Capri M, Salvioli S, Taupin JL, Garagnani P, Franceschi C 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...
Source: Ageing Research Reviews - Category: Genetics & Stem Cells Authors: Tags: Ageing Res Rev Source Type: research