DCAF1 regulates Treg senescence via the ROS axis during immunological aging

Guo, Zengli; Wang, Gang; Wu, Bing; Chou, Wei-Chun; Cheng, Liang; Zhou, Chenlin; Lou, Jitong; Wu, Di; Su, Lishan; Zheng, Junnian; Ting, Jenny P.‐Y.; Wan, Yisong Y.

doi:10.1172/jci136466

Cited by 87 publications

(74 citation statements)

References 67 publications

(94 reference statements)

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“…Aging-related changes have also been reported in cytotoxic T cells and regulatory T cells (Tregs) that act in concert to provide T cell-mediated immunity [ 32 , 33 ]. Tregs have functions that suppress immune responses activated by conventional T cells [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Chemokines Up-Regulated in Epithelial Cells Control Senescence-Associated T Cell Accumulation in Salivary Glands of Aged and Sjögren’s Syndrome Model Mice

Kurosawa

Shikama

Furukawa

et al. 2021

IJMS

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Immunosenescence is characterized by age-associated changes in immunological functions. Although age- and autoimmune-related sialadenitis cause dry mouth (xerostomia), the roles of immunosenescence and cellular senescence in the pathogenesis of sialadenitis remain unknown. We demonstrated that acquired immune cells rather than innate immune cells infiltrated the salivary glands (SG) of aged mice. An analysis of isolated epithelial cells from SG revealed that the expression levels of the chemokine CXCL13 were elevated in aged mice. Senescence-associated T cells (SA-Ts), which secrete large amounts of atypical pro-inflammatory cytokines, are involved in the pathogenesis of metabolic disorders and autoimmune diseases. The present results showed that SA-Ts and B cells, which express the CXCL13 receptor CXCR5, accumulated in the SG of aged mice, particularly females. CD4+ T cells derived from aged mice exhibited stronger in vitro migratory activity toward CXCL13 than those from young mice. In a mouse model of Sjögren’s syndrome (SS), SA-Ts also accumulated in SG, presumably via CXCL12-CXCR4 signaling. Collectively, the present results indicate that SA-Ts accumulate in SG, contribute to the pathogenesis of age- and SS-related sialadenitis by up-regulating chemokines in epithelial cells, and have potential as therapeutic targets for the treatment of xerostomia caused by these types of sialadenitis.

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Section: Discussionmentioning

confidence: 99%

Chemokines Up-Regulated in Epithelial Cells Control Senescence-Associated T Cell Accumulation in Salivary Glands of Aged and Sjögren’s Syndrome Model Mice

Kurosawa

Shikama

Furukawa

et al. 2021

IJMS

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“…ROS generation results in Treg cell-mediated immunosuppression and limits anti-tumor T cell response in the tumor microenvironment ( 69 ). Reduced ROS generation impairs Treg function and differentiation, and it is suggested that ROS is required for the suppressive function of Treg cells ( 69 , 96 ). In an exogenous H 2 O 2 environment, Treg cells are more resistant to oxidative-induced death compared to Teff cells and memory T cells ( 97 ).…”

Section: T Cell Differentiation Impacted By Rosmentioning

confidence: 99%

“…In an exogenous H 2 O 2 environment, Treg cells are more resistant to oxidative-induced death compared to Teff cells and memory T cells ( 97 ). ROS generation is found to be greater in Treg cells in comparison to Teff cells ( 96 ). Excessive ROS levels have been observed in aged Treg cells from >18-month-year-old mice, whereas young Treg cells exhibit controlled ROS generation, normal proliferation, and controlled inflammation ( 96 ).…”

Section: T Cell Differentiation Impacted By Rosmentioning

confidence: 99%

“…ROS generation is found to be greater in Treg cells in comparison to Teff cells ( 96 ). Excessive ROS levels have been observed in aged Treg cells from >18-month-year-old mice, whereas young Treg cells exhibit controlled ROS generation, normal proliferation, and controlled inflammation ( 96 ). Limitation of ROS generation by ROS scavenger NAC has been shown to promote proliferation and survival in aged Treg cells ( 96 ).…”

Section: T Cell Differentiation Impacted By Rosmentioning

confidence: 99%

“…Excessive ROS levels have been observed in aged Treg cells from >18-month-year-old mice, whereas young Treg cells exhibit controlled ROS generation, normal proliferation, and controlled inflammation ( 96 ). Limitation of ROS generation by ROS scavenger NAC has been shown to promote proliferation and survival in aged Treg cells ( 96 ). Henceforth, the phenotypic connection between ROS generation and Treg cell differentiation is found.…”

Section: T Cell Differentiation Impacted By Rosmentioning

confidence: 99%

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Metabolic Reprogramming and Reactive Oxygen Species in T Cell Immunity

et al. 2021

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T cells undergo metabolic reprogramming and multiple biological processes to satisfy their energetic and biosynthetic demands throughout their lifespan. Several of these metabolic pathways result in the generation of reactive oxygen species (ROS). The imbalance between ROS generation and scavenging could result in severe damage to the cells and potential cell death, ultimately leading to T cell-related diseases. Interestingly, ROS play an essential role in T cell immunity. Here, we introduce the important connectivity between T cell lifespan and the metabolic reprogramming among distinct T cell subsets. We also discuss the generation and sources of ROS production within T cell immunity as well as highlight recent research concerning the effects of ROS on T cell activities.

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Cellular senescence and metabolic reprogramming: Unraveling the intricate crosstalk in the immunosuppressive tumor microenvironment

Zhang,

Guo,

et al. 2024

Cancer Communications

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The intrinsic oncogenic mechanisms and properties of the tumor microenvironment (TME) have been extensively investigated. Primary features of the TME include metabolic reprogramming, hypoxia, chronic inflammation, and tumor immunosuppression. Previous studies suggest that senescence‐associated secretory phenotypes that mediate intercellular information exchange play a role in the dynamic evolution of the TME. Specifically, hypoxic adaptation, metabolic dysregulation, and phenotypic shifts in immune cells regulated by cellular senescence synergistically contribute to the development of an immunosuppressive microenvironment and chronic inflammation, thereby promoting the progression of tumor events. This review provides a comprehensive summary of the processes by which cellular senescence regulates the dynamic evolution of the tumor‐adapted TME, with focus on the complex mechanisms underlying the relationship between senescence and changes in the biological functions of tumor cells. The available findings suggest that components of the TME collectively contribute to the progression of tumor events. The potential applications and challenges of targeted cellular senescence‐based and combination therapies in clinical settings are further discussed within the context of advancing cellular senescence‐related research.

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DCAF1 regulates Treg senescence via the ROS axis during immunological aging

Cited by 87 publications

References 67 publications

Chemokines Up-Regulated in Epithelial Cells Control Senescence-Associated T Cell Accumulation in Salivary Glands of Aged and Sjögren’s Syndrome Model Mice

Chemokines Up-Regulated in Epithelial Cells Control Senescence-Associated T Cell Accumulation in Salivary Glands of Aged and Sjögren’s Syndrome Model Mice

Metabolic Reprogramming and Reactive Oxygen Species in T Cell Immunity

Cellular senescence and metabolic reprogramming: Unraveling the intricate crosstalk in the immunosuppressive tumor microenvironment

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