Activation of immunosuppressive network in the aging process
Antero Salminen Ageing Research Reviews Volume 57, January 2020, 100998
Highlights
• Chronic low-grade inflammation, called inflammaging, is a hallmark of aging process.
• Aging is associated with the states called anti-inflammaging and immunosenescence.
• Immunosuppressive cells inhibit functions of myeloid and lymphoid effector cells.
• Aging increases the activity of the regulatory cells of immunosuppressive network.
• Immunosuppressive network induces remodeling of immune system with aging.
Chronic low-grade inflammation has a key role in the aging process, a state called inflammaging. It is known that the chronic inflammatory condition generates counteracting immunosuppressive state in many diseases. Inflammaging is also associated with an immune deficiency; generally termed as immunosenescence, although it is not known whether it represents the senescence of immune cells or the active remodeling of immune system. Evidence has accumulated since the 1970′s indicating that immunosenescence might be caused by an increased activity of immunosuppressive cells rather than cellular senescence. Immune cells display remarkable plasticity; many of these cells can express both proinflammatory and immunosuppressive phenotypes in a context-dependent manner. The immunosuppressive network involves the regulatory subtypes of T (Treg) and B (Breg) cells as well as regulatory phenotypes of macrophages (Mreg), dendritic (DCreg), natural killer (NKreg), and type II natural killer T (NKT) cells. The immunosuppressive network also includes monocytic (M-MDSC) and polymorphonuclear (PMN-MDSC) myeloid-derived suppressor cells which are immature myeloid cells induced by inflammatory mediators. This co-operative network is stimulated in chronic inflammatory conditions preventing excessive inflammatory responses but at the same time they exert harmful effects on the immune system and tissue homeostasis. Recent studies have revealed that the aging process is associated with the activation of immunosuppressive network, especially the functions of MDSCs, Tregs, and Mregs are increased. I will briefly review the properties of the regulatory phenotypes of immune cells and examine in detail the evidences for an activation of immunosuppressive network with aging.
