ArticleProceedings of the National Academy of Sciences of the United States of America2012
Signal inhibition by the dual-specific phosphatase 4 impairs T cell-dependent B-cell responses with age.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 98 citations in OpenAlex.
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- A silver bullet for ageing medicine?: clinical relevance of T-cell checkpoint receptors in normal human ageing.Frontiers in immunology · 2024Review
- Accumulation of immune-suppressive CD4 + T cells in aging - tempering inflammaging at the expense of immunity.Seminars in immunology · 2023Review
- An integrative analysis of the single-cell transcriptome identifies DUSP4 as an exhaustion-associated gene in tumor-infiltrating CD8+ T cells.Functional & integrative genomics · 2023Article
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- AgeAnno: a knowledgebase of single-cell annotation of aging in human.Nucleic acids research · 2023Article
- Transcriptomic profiles of multiple organ dysfunction syndrome phenotypes in pediatric critical influenza.Frontiers in immunology · 2023Article
- Age-dependent immune responses in COVID-19-mediated liver injury: focus on cytokines.Frontiers in endocrinology · 2023Review
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- How Can We Improve the Vaccination Response in Older People? Part II: Targeting Immunosenescence of Adaptive Immunity Cells.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
T cell-dependent B-cell responses decline with age, suggesting defective CD4 T-cell function. CD4 memory T cells from individuals older than 65 y displayed increased and sustained transcription of the dual-specific phosphatase 4 (DUSP4) that shortened expression of CD40-ligand (CD40L) and inducible T-cell costimulator (ICOS) (both P < 0.001) and decreased production of IL-4, IL-17A, and IL-21 (all P < 0.001) after in vitro activation. In vivo after influenza vaccination, activated CD4 T cells from elderly individuals had increased DUSP4 transcription (P = 0.002), which inversely correlated with the expression of CD40L (r = 0.65, P = 0.002), ICOS (r = 0.57, P = 0.008), and IL-4 (r = 0.66, P = 0.001). In CD4 KO mice reconstituted with DUSP4 OT-II T cells, DUSP4 had a negative effect on the expansion of antigen-specific B cells (P = 0.003) and the production of ova-specific antibodies (P = 0.03) after immunization. Silencing of DUSP4 in memory CD4 T cells improved CD40L (P < 0.001), IL-4 (P = 0.007), and IL-21 (P = 0.04) expression significantly more in the elderly than young adults. Consequently, the ability of CD4 memory T cells to support B-cell differentiation that was impaired in the elderly (P = 0.004) was restored. Our data suggest that increased DUSP4 expression in activated T cells in the elderly in part accounts for defective adaptive immune responses.
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Registered trials
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