TY - JOUR
T1 - Disorganization of secondary lymphoid organs and dyscoordination of chemokine secretion as key contributors to immune aging
AU - Sonar, Sandip Ashok
AU - Watanabe, Makiko
AU - Nikolich, Janko
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/11
Y1 - 2023/11
N2 - Aging is characterized by progressive loss of organ and tissue function, and the immune system is no exception to that inevitable principle. Of all the age-related changes in the body, reduction of the size of, and naïve T (Tn) cell output from, the thymus occurs earliest, being prominent already before or by the time of puberty. Therefore, to preserve immunity against new infections, over much of their lives, vertebrates dominantly rely on peripheral maintenance of the Tn cell pool in the secondary lymphoid organs (SLO). However, SLO structure and function subsequently also deteriorate with aging. Several recent studies have made a convincing case that this deterioration is of major importance to the erosion of protective immunity in the last third of life. Specifically, the SLO were found to accumulate multiple degenerative changes with aging. Importantly, the results from adoptive transfer and parabiosis studies teach us that the old microenvironment is the limiting factor for protective immunity in old mice. In this review, we discuss the extent, mechanisms, and potential role of stromal cell aging in the age-related alteration of T cell homeostatic maintenance and immune function decline. We use that discussion to frame the potential strategies to correct the SLO stromal aging defects - in the context of other immune rejuvenation approaches, - to improve functional immune responses and protective immunity in older adults.
AB - Aging is characterized by progressive loss of organ and tissue function, and the immune system is no exception to that inevitable principle. Of all the age-related changes in the body, reduction of the size of, and naïve T (Tn) cell output from, the thymus occurs earliest, being prominent already before or by the time of puberty. Therefore, to preserve immunity against new infections, over much of their lives, vertebrates dominantly rely on peripheral maintenance of the Tn cell pool in the secondary lymphoid organs (SLO). However, SLO structure and function subsequently also deteriorate with aging. Several recent studies have made a convincing case that this deterioration is of major importance to the erosion of protective immunity in the last third of life. Specifically, the SLO were found to accumulate multiple degenerative changes with aging. Importantly, the results from adoptive transfer and parabiosis studies teach us that the old microenvironment is the limiting factor for protective immunity in old mice. In this review, we discuss the extent, mechanisms, and potential role of stromal cell aging in the age-related alteration of T cell homeostatic maintenance and immune function decline. We use that discussion to frame the potential strategies to correct the SLO stromal aging defects - in the context of other immune rejuvenation approaches, - to improve functional immune responses and protective immunity in older adults.
KW - Immune aging
KW - Lymph node involution
KW - Lymphoid stromal cells
KW - Secondary lymphoid organs
KW - T cell homeostasis
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U2 - 10.1016/j.smim.2023.101835
DO - 10.1016/j.smim.2023.101835
M3 - Review article
C2 - 37651849
AN - SCOPUS:85169017683
SN - 1044-5323
VL - 70
JO - Seminars in Immunology
JF - Seminars in Immunology
M1 - 101835
ER -