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Review
. 2019 May;76(10):1901-1918.
doi: 10.1007/s00018-019-03048-x. Epub 2019 Feb 20.

Immunosenescence: The Potential Role of Myeloid-Derived Suppressor Cells (MDSC) in Age-Related Immune Deficiency

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Free PMC article
Review

Immunosenescence: The Potential Role of Myeloid-Derived Suppressor Cells (MDSC) in Age-Related Immune Deficiency

Antero Salminen et al. Cell Mol Life Sci. .
Free PMC article

Abstract

The aging process is associated with chronic low-grade inflammation in both humans and rodents, commonly called inflammaging. At the same time, there is a gradual decline in the functional capacity of adaptive and innate immune systems, i.e., immunosenescence, a process not only linked to the aging process, but also encountered in several pathological conditions involving chronic inflammation. The hallmarks of immunosenescence include a decline in the numbers of naïve CD4+ and CD8+ T cells, an imbalance in the T cell subsets, and a decrease in T cell receptor (TCR) repertoire and signaling. Correspondingly, there is a decline in B cell lymphopoiesis and a reduction in antibody production. The age-related changes are not as profound in innate immunity as they are in adaptive immunity. However, there are distinct functional deficiencies in dendritic cells, natural killer cells, and monocytes/macrophages with aging. Interestingly, the immunosuppression induced by myeloid-derived suppressor cells (MDSC) in diverse inflammatory conditions also targets mainly the T and B cell compartments, i.e., inducing very similar alterations to those present in immunosenescence. Here, we will compare the immune profiles induced by immunosenescence and the MDSC-driven immunosuppression. Given that the appearance of MDSCs significantly increases with aging and MDSCs are the enhancers of other immunosuppressive cells, e.g., regulatory T cells (Tregs) and B cells (Bregs), it seems likely that MDSCs might remodel the immune system, thus preventing excessive inflammation with aging. We propose that MDSCs are potent inducers of immunosenescence.

Keywords: Aging; Cellular senescence; Immunotherapy; Myelopoiesis; Rejuvenation; Trained immunity.

Conflict of interest statement

The authors state that there are no personal or institutional conflicts of interest.

Figures

Fig. 1
Fig. 1
A schematic representation of MDSC-driven immunosenescence. The age-related cellular stress and senescence induce a condition termed inflammaging, which is associated with increased myelopoiesis. A mild inflammatory profile stimulates the production of MDSCs and other immunosuppressive cells, e.g., Tregs, Bregs, and Mregs. The cooperation between the components of this immunosuppressive network creates an immune-suppressive microenvironment, which after the remodeling of the immune system generates immunosenescence
Fig. 2
Fig. 2
The comparison of immune cell phenotypes induced by MDSC-driven immunosuppression (upper panel) and age-related immunosenescence (lower panel)

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