Increased immunosuppression impairs tissue homeostasis with aging and age-related diseases.
J Mol Med (Berl)
; 99(1): 1-20, 2021 01.
Article
en En
| MEDLINE
| ID: mdl-33025106
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 anti-inflammaging 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-ß 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-ß 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Envejecimiento
/
Tolerancia Inmunológica
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Mol Med (Berl)
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Finlandia