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FOXP3 protects conventional human T cells from premature restimulation-induced cell death

Cellular & Molecular Immunology 2021年第1期18卷 194-205页

作者： 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 Department of Pharmacology&Molecular Therapeutics Uniformed Services University of the Health SciencesBethesdaMD 20817USA The American Genome Center(TAGC) Collaborative Health Initiative Research ProgramUniformed Services University of the Health SciencesBethesdaMDUSA Department of Anatomy Physiology&GeneticsUniformed Services University of the Health SciencesBethesdaMDUSA

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.

关键词： conventional T cells RICD FOXP3 autophagy CD48

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Determination of the Toxicological Risk of Urban Waste from the City of Uvira Dumped into the North-Western Coast in lake Tanganyika (Democratic Republic of Congo)

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Journal of Environmental Protection 2021年第10期12卷 677-693页

作者： Lumami Kapepula Vercus Théophile Ndikumana Njoyim Estella Buleng Tamungang Musibono Dieu-Donné Lukusa Mbaya Alain Nsimanda Ipey camille Patricia Luis Alconero Bart Van Der Bruggen Department of Hydrology Hydrobiology Research Center Uvira R.D. Congo Department of Chemistry University of Burundi Bujumbura Burundi Doctoral School of the University of Burundi Bujumbura Burundi Materials & Process Engineering (IMAP) Catholic University of Louvain Place Sainte Barbe 2 B-1348 Louvain-la-Neuve Belgium Department of Chemistry Faculty of Science University of Dschang Dschang Cameroon Department of Chemistry Higher Teacher Training College The University of Bamenda Bamenda Cameroon Department of the Environment University of Kinshasa Kinshasa D.R. Congo Process Engineering for Sustainable Systems (ProcESS) Katholieke Universiteit Leuven Celestijnenlaan 200f 3001 Leuven Belgium Faculty of Engineering and the Built Environment Tshwane University of Technology Pretoria South Africa

This study focuses on determining the toxicological risks of urban waste from the city of Uvira, discharged into lake Tanganyika, on the surrounding population. Volatile organic compounds were measured in a variety of solid waste matrices, including inorganic micropollutants in wastewater and fish. The concentrations of Hg and Pb in the lake were found to be 1.21 and 1.42 μg/L respectively and between 0.83 to 18.36 μg/L of Hg and 8.25 to 670 μg/L of Pb, at the collector outlet. The presence of trace metallic elements, such as Cr, Co, Ni, Cu, Zn, As, Sb, Hg and Pb, were detected at high concentrations compared to the WHO standard. An ecotoxicology experiment herein on wastewater samples showed lethal pollutant concentrations of the order of 0.0055 mL/mL which killed at least 50% of fish (LC50), confirming the toxicity of the wastewater. These potentially harmful effluents also contain volatile organic compounds originating in high concentration from the pharmaceutical discharges of the general Uvira hospital, in particular: toluene, ethylbenzene, m-xylene/p-xylene, o-xylene and chloroform in higher concentrations compared to the norm. Other components such as benzene, bromodichloroethane and 1,1-dichloroethane were found to be present, but at a concentration below 0.05 ppb. A variety of trace organics can be suspected to be present as well.

关键词： lake Tanganyika Lethal Dose Volatile Organic Compounds Heavy Metals Water Pollution

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