Disorganization of secondary lymphoid organs and dyscoordination of chemokine secretion as key contributors to immune aging

Sonar, Sandip Ashok; Watanabe, Makiko; Nikolich, Janko Ž.

doi:10.1016/j.smim.2023.101835

Cited by 4 publications

(1 citation statement)

References 197 publications

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“…Indeed, studies have shown a strong skewing in the murine CD8 + T cell pool of unimmunized mice due to peripheral selection ( 18 ). Moreover, newly produced T cells derived from thymic reconstitution have difficulty in being seeded in the periphery in older mice ( 19 , 20 ). Such a fitness selection might change the composition of naive T cells with age and be particularly evident in single-cell studies.…”

Section: Introductionmentioning

confidence: 99%

PREX1 improves homeostatic proliferation to maintain a naïve CD4 T cell compartment in older age

Zhang,

Okuyama,

Jain

et al. 2024

JCI Insight

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The human adult immune system maintains normal T cell counts and compensates for T cell loss throughout life, mainly through peripheral homeostatic proliferation after the ability of the thymus to generate new T cells has rapidly declined at adolescence. This process is mainly driven by STAT5-activating cytokines, most importantly IL-7, and is very effective in maintaining a large naive CD4 + T cell compartment into older age. Here, we describe that naive CD4 + T cells undergo adaptations to optimize IL-7 responses by upregulating the guanine-nucleotide exchange factor PREX1 in older age. PREX1 promotes nuclear translocation of phosphorylated STAT5, thereby supporting homeostatic proliferation in response to IL-7. Through the same mechanism, increased expression of PREX1 also biases naive cells to differentiate into effector T cells. These findings are consistent with the concept that primarily beneficial adaptations during aging, i.e., improved homeostasis, account for unfavorable functions of the aged immune system, in this case biased differentiation.

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Section: Introductionmentioning

confidence: 99%

PREX1 improves homeostatic proliferation to maintain a naïve CD4 T cell compartment in older age

Zhang,

Okuyama,

Jain

et al. 2024

JCI Insight

View full text Add to dashboard Cite

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Nurture over nature for old antitumor T cells

Wilson,

Nikolich

2024

Nat Immunol

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Higher blood manganese level associated with increased risk of adult latent tuberculosis infection in the US population

Qi,

Zhang,

2024

Front. Public Health

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BackgroundThe associations between blood heavy metal levels and latent tuberculosis infection (LTBI) have not been fully elucidated. The aim of this study was to investigate the potential association between blood heavy metal levels and LTBI in adults using National Health and Nutrition Examination Survey data from 2011 to 2012.MethodsWe enrolled 1710 participants in this study, and compared the baseline characteristics of participants involved. Multivariate logistic regression analysis, restricted cubic splines (RCS) analysis, along with subgroup analysis and interaction tests were utilized to explore the association between blood manganese (Mn) level and LTBI risk.ResultsParticipants with LTBI had higher blood Mn level compared to non-LTBI individuals (p < 0.05), while the levels of lead, cadmium, total mercury, selenium, copper, and zinc did not differ significantly between the two groups (p > 0.05). In the fully adjusted model, a slight increase in LTBI risk was observed with each 1-unit increase in blood Mn level (OR = 1.00, 95% CI: 1.00–1.01, p = 0.02). Participants in the highest quartile of blood Mn level had a threefold increase in LTBI risk compared to those in the lowest quartile (OR = 4.01, 95% CI: 1.22–11.33, p = 0.02). RCS analysis did not show a non-linear relationship between blood Mn level and LTBI (non-linear p-value = 0.0826). Subgroup analyses and interaction tests indicated that age, alcohol consumption, and income-to-poverty ratio significantly influenced LTBI risk (interaction p-values<0.05).ConclusionIndividuals with LTBI had higher blood Mn level compared to non-LTBI individuals, and higher blood Mn level associated with increased LTBI risk.

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Disorganization of secondary lymphoid organs and dyscoordination of chemokine secretion as key contributors to immune aging

Cited by 4 publications

References 197 publications

PREX1 improves homeostatic proliferation to maintain a naïve CD4 T cell compartment in older age

PREX1 improves homeostatic proliferation to maintain a naïve CD4 T cell compartment in older age

Nurture over nature for old antitumor T cells

Higher blood manganese level associated with increased risk of adult latent tuberculosis infection in the US population

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