Immune‑Ageing Evaluation of Peripheral T and NK Lymphocyte Subsets in Chinese Healthy Adults

Ageing is often accompanied with a decline in immune system function,resulting in immune ageing.Numerous studies have focussed on the changes in different lymphocyte subsets in diseases and immunosenescence.The change in immune phenotype is a key indication of the diseased or healthy status.However,the changes in lymphocyte number and phenotype brought about by ageing have not been comprehensively analysed.Here,we analysed T and natural killer(NK)cell subsets,the phenotype and cell differentiation states in 43,096 healthy individuals,aged 20–88 years,without known diseases.Thirty-six immune parameters were analysed and the reference ranges of these subsets were established in different age groups divided into 5-year intervals.The data were subjected to random forest machine learning for immune-ageing modelling and confirmed using the neural network analysis.Our initial analysis and machine modelling prediction showed that na.ve T cells decreased with ageing,whereas central memory T cells(Tcm)and effector memory T cells(Tem)increased cluster of differentiation(CD)28-associated T cells.This is the largest study to investigate the correlation between age and immune cell function in a Chinese population,and provides insightful differences,suggesting that healthy adults might be considerably influenced by age and sex.The age of a person's immune system might be different from their chronological age.Our immune-ageing modelling study is one of the largest studies to provide insights into‘immune-age’rather than‘biological-age’.Through machine learning,we identified immune factors influencing the most through ageing and built a model for immune-ageing prediction.Our research not only reveals the impact of age on immune parameter differences within the Chinese population,but also provides new insights for monitoring and preventing some diseases in clinical practice.

The molecular mechanisms supporting the homeostasis and activation of dendritic epidermal T cell and its role in promoting wound healing

The epidermis is the outermost layer of skin and the first barrier against invasion.Dendritic epidermal T cells(DETCs)are a subset ofT cells and an important component of the epidermal immune microenvironment.DETCs are involved in skin wound healing,malignancy and autoim-mune diseases.DETCs secrete insulin-like growth factor-1 and keratinocyte growth factor for skin homeostasis and re-epithelization and release inflammatory factors to adjust the inflammatory microenvironment of wound healing.Therefore,an understanding of their development,activation and correlative signalling pathways is indispensable for the regulation of DETCs to accelerate wound healing.Our review focuses on the above-mentioned molecular mechanisms to provide a general research framework to regulate and control the function of DETCs.

LncRNA MIAT impairs cardiac contractile function by acting on mitochondrial translocator protein TSPO in a mouse model of myocardial infarction

Dear Editor,Long non-coding RNA MIAT(IncR-MIAT)has recently been identified as a risk factor for myocardial infarction(Ml).1 However,how IncR-MIAT controls Ml remained yet to be determined.To shed light on this issue,we firstly detected the expression of IncR-MIAT using qRT-PCR and found a robust elevation(>5-fold)of IncR-MIAT level in heart of Ml mice relative to sham-operated control counterparts(Supplementary Fig.S1a). MIAT in NMVCs(Supplementary Fig.Sic).

Mitochondria-targeting polydopamine-coated nanodrugs for effective photothermal-and chemo-synergistic therapies against lung cancer

Targetingmitochondria via nano platform emerged as an attractive anti-tumor pathway due to the central regulation role in cellar apoptosis and drug resistance.Here,a mitochondria-targeting nanoparticle(TOS-PDA-PEG-TPP)was designed to precisely deliver polydopamine(PDA)as the photothermal agent and alphatocopherol succinate(α-TOS)as the chemotherapeutic drug to the mitochondria of the tumor cells,which inhibits the tumor growth through chemo-and photothermal-synergistic therapies.TOSPDA-PEG-TPP was constructed by coating PDA on the surface of TOS NPs self-assembled byα-TOS,followed by grafting PEGand triphenylphosphonium(TPP)on their surface to prolong the blood circulation time and target delivery of TOS and PDA to the mitochondria of tumor cells.In vitro studies showed that TOS-PDA-PEGTPP could be efficiently internalized by tumor cells and accumulated atmitochondria,resulting in cellular apoptosis and synergistic inhibition of tumor cell proliferation.In vivo studies demonstrated that TOS-PDA-PEG-TPP could be efficiently localized at tumor sites and significantly restrain the tumor growth under NIR irradiation without apparent toxicity or deleterious effects.Conclusively,the combination strategy adopted for functional nanodrugs construction aimed at target-delivering therapeutic agents with different action mechanisms to the same intracellular organelles can be extended to other nanodrugs-dependent therapeutic systems.

Metabolic Control ofγδT Cell Function

Metabolic change is associated with cell activities,such as signal transduction,cell differentiation,and cell cycle.In the pathogenesis of autoimmune diseases,abnormal activation of T cells is often accompanied by changes in their metabolism.Conversely,the changes of metabolites can also regulate the proliferation,differentiation,and function of T cells.As a bridge between innate and adaptive immune responses,γδT cells have unique biological characteristics and functions.However,the immunometabolic mechanism ofγδT cells has been a novel field for research in recent years.In this review,we summarize the influence of metabolic pathways and nutrients onγδT cell function,and metabolic features ofγδT cell subsets,which may provide new insights in interventions targetingγδT cells in disease control.