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1篇 您的检索式:作者名="Gauthaman Sukumar"
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1FOXP3 protects conventional human T cells from premature restimulation-induced cell death显示文摘The adaptive immune response relies on specific apoptotic programs to maintain homeostasis.Conventional effector T cell(Tcon)expansion is constrained by both forkhead box P3(FOXP3)^(+)-regulatory T cells(Tregs)and restimulation-induced cell death(RICD),a proprlocidal apoptosis pathway triggered by repeated stimulation through the T-cell receptor(TCR).Constitutive FOXP3 expression protects Tregs from RICD by suppressing SLAM-associated protein(SAP),a key adaptor protein that amplifies TCR signaling strength.The role of transient FOXP3 induction in activated human CD4 and CD8 Tcons remains unresolved,but its expression is inversely correlated with acquired RICD sensitivity.Here,we describe a novel role for FOXP3 In protecting human Tcons from premature RICD during expansion.Unlike FOXP3-mediated protection from RICD in Tregs,FOXP3 protects Tcons through a distinct mechanism requiring de novo transcription that does not require SAP suppression.Transcriptome profiling and functional analyses of expanding Tcons revealed that FOXP3 enhances expression of the SLAM family receptor CD48,which in turn sustains basal autophagy and suppresses pro-apoptotic p53 signaling.Both CD48 and FOXP3 expression reduced p53 accumulation upon TCR restimulation.Furthermore,silencing FOXP3 expression or blocking CD48 decreased the mitochondrial membrane potential in expanding Tcons with a concomitant reduction in basal autophagy.Our findings suggest that FOXP3 governs a distinct transcriptional program in early-stage effector Tcons that maintains RICD resistance via CD48-dependent protective autophagy and p53 suppression.Kelsey Voss Camille Lake Christopher R.Luthers Nathaniel M.Lott Batsukh Dorjbal Swadhinya Arjunaraja Bradly M.Bauman Anthony R.Soltis Gauthaman Sukumar Clifton LDalgard Andrew L.Snow 2021Cellular & Molecular Immunology2021,18,1:0
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