Increased immunosuppression impairs tissue homeostasis with aging and age-related diseases
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REVIEW
Increased immunosuppression impairs tissue homeostasis with aging and age-related diseases Antero Salminen 1 Received: 1 June 2020 / Revised: 21 September 2020 / Accepted: 29 September 2020 # The Author(s) 2020
Abstract Chronic low-grade inflammation is a common hallmark of the aging process and many age-related diseases. There is substantial evidence that persistent inflammation is associated with a compensatory anti-inflammatory response which prevents excessive tissue damage. Interestingly, the inflammatory state encountered with aging, called inflammaging, is associated with the antiinflammaging process. The age-related activation of immunosuppressive network includes an increase in the numbers of myeloid-derived suppressor cells (MDSC), regulatory T cells (Treg), and macrophages (Mreg/M2c). Immunosuppressive cells secrete several anti-inflammatory cytokines, e.g., TGF-β and IL-10, as well as reactive oxygen and nitrogen species (ROS/RNS). Moreover, immunosuppressive cells suppress the function of effector immune cells by catabolizing L-arginine and tryptophan through the activation of arginase 1 (ARG1) and indoleamine 2,3-dioxygenase (IDO), respectively. Unfortunately, the immunosuppressive armament also induces harmful bystander effects in neighboring cells by impairing host tissue homeostasis. For instance, TGF-β signaling can trigger many age-related degenerative changes, e.g., cellular senescence, fibrosis, osteoporosis, muscle atrophy, and the degeneration of the extracellular matrix. In addition, changes in the levels of ROS, RNS, and the metabolites of the kynurenine pathway can impair tissue homeostasis. This review will examine in detail the harmful effects of the immunosuppressive cells on host tissues. It seems that this age-related immunosuppression prevents inflammatory damage but promotes the tissue degeneration associated with aging and age-related diseases. Key messages • Low-grade inflammation is associated with the aging process and age-related diseases. • Persistent inflammation activates compensatory immunosuppression with aging. • The numbers of immunosuppressive cells increase with aging and age-related diseases. • Immunosuppressive mechanisms evoke harmful bystander effects in host tissues. • Immunosuppression promotes tissue degeneration with aging and age-related diseases. Keywords Aging . Alzheimer’s . Immunometabolism . Immunosenescence . Nitric oxide . Tissue degeneration
Introduction The remodeling of the immune system including the presence of chronic low-grade inflammation is one hallmark of the aging process [1, 2]. This age-related immune state has commonly been called inflammaging. Systemic chronic inflammation has also been implicated in many age-related diseases,
* Antero Salminen [email protected] 1
Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland
aggravating the pathology of these diseases, e.g., cardiovascular diseases, chronic kidney disease, non-alcoholic fatty liver disease
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