2023
Sodium perturbs mitochondrial respiration and induces dysfunctional Tregs
Côrte-Real B, Hamad I, Arroyo Hornero R, Geisberger S, Roels J, Van Zeebroeck L, Dyczko A, van Gisbergen M, Kurniawan H, Wagner A, Yosef N, Weiss S, Schmetterer K, Schröder A, Krampert L, Haase S, Bartolomaeus H, Hellings N, Saeys Y, Dubois L, Brenner D, Kempa S, Hafler D, Stegbauer J, Linker R, Jantsch J, Müller D, Kleinewietfeld M. Sodium perturbs mitochondrial respiration and induces dysfunctional Tregs. Cell Metabolism 2023, 35: 299-315.e8. PMID: 36754020, DOI: 10.1016/j.cmet.2023.01.009.Peer-Reviewed Original ResearchConceptsHuman TregsPro-inflammatory featuresLong-term dysfunctionPro-inflammatory signatureMetabolic reprogrammingLong-term functionDysfunctional TregsFoxp3 downregulationPeripheral toleranceMitochondrial respirationMetabolic disturbancesTregsImmune functionAutoimmunityMetabolic fitnessIntracellular NaMitochondrial NaHigh saltMitochondrial metabolismElectron transport chainTranscriptional changesFoxp3DysfunctionBlockade
2021
The double-edged sword: Harnessing PD-1 blockade in tumor and autoimmunity
Kuchroo JR, Hafler DA, Sharpe AH, Lucca LE. The double-edged sword: Harnessing PD-1 blockade in tumor and autoimmunity. Science Immunology 2021, 6: eabf4034. PMID: 34739340, DOI: 10.1126/sciimmunol.abf4034.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsPD-1 blockadeRegulatory T cell functionImmune checkpoint blockadeCheckpoint blockade immunotherapyT cell responsesT cell functionBlockade immunotherapyAdverse eventsAntitumor immunityCheckpoint blockadeCell responsesBlockadeCell functionAutoimmunityMechanistic featuresEdged swordImmunotherapyTumorsCancerImmunity
2004
PD-1 ligands, negative regulators for activation of naïve, memory, and recently activated human CD4+ T cells
Cai G, Karni A, Oliveira EM, Weiner HL, Hafler DA, Freeman GJ. PD-1 ligands, negative regulators for activation of naïve, memory, and recently activated human CD4+ T cells. Cellular Immunology 2004, 230: 89-98. PMID: 15598424, DOI: 10.1016/j.cellimm.2004.09.004.Peer-Reviewed Original ResearchConceptsPD-1 ligand blockadeT cellsPD-L1Myelin basic proteinPD-L2Human CD4Ex vivo dendritic cellsVivo dendritic cellsPD-1 ligandsPD-1 pathwayPrimary responseActivation of naïveNaive T cellsPD-1Dendritic cellsCytokine productionNormal donorsIFN-gammaSecondary responseCD4BlockadeHigh expressionNegative regulatory pathwaysInduced activationBasic protein