Rodriguez-Barbosa, Jose-IgnacioSchneider, PascalGraca, LuisBühler, LeoPerez-Simon, Jose-Antoniodel Rio, Maria-Luisa2022-07-042022-07-042020-05-09Rodriguez-Barbosa JI, Schneider P, Graca L, Bühler L, Perez-Simon JA, del Rio ML. The Role of TNFR2 and DR3 in the In Vivo Expansion of Tregs in T Cell Depleting Transplantation Regimens. Int J Mol Sci. 2020 May 9;21(9):3347http://hdl.handle.net/10668/3738Regulatory T cells (Tregs) are essential for the maintenance of tolerance to self and non-self through cell-intrinsic and cell-extrinsic mechanisms. Peripheral Tregs survival and clonal expansion largely depend on IL-2 and access to co-stimulatory signals such as CD28. Engagement of tumor necrosis factor receptor (TNFR) superfamily members, in particular TNFR2 and DR3, contribute to promote peripheral Tregs expansion and sustain their survival. This property can be leveraged to enhance tolerance to allogeneic transplants by tipping the balance of Tregs over conventional T cells during the course of immune reconstitution. This is of particular interest in peri-transplant tolerance induction protocols in which T cell depletion is applied to reduce the frequency of alloreactive T cells or in conditioning regimens that allow allogeneic bone marrow transplantation. These conditioning regimens are being implemented to limit long-term side effects of continuous immunosuppression and facilitate the establishment of a state of donor-specific tolerance. Lymphopenia-induced homeostatic proliferation in response to cytoreductive conditioning is a window of opportunity to enhance preferential expansion of Tregs during homeostatic proliferation that can be potentiated by agonist stimulation of TNFR.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Regulatory T cellsLymphopeniaHomeostatic proliferationTransplantationTNF/TNF receptorsGraft-versus-host diseaseGraft rejectionLinfocitos T reguladoresLinfopeniaProliferación celularTrasplanteReceptores del factor de necrosis tumoralEnfermedad injerto contra huéspedRechazo de injertoMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immunologic Techniques::Immunization::Immunization, Passive::Adoptive TransferMedical Subject Headings::Anatomy::Body Regions::Transplants::AllograftsMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell DifferentiationMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::Growth::Cell Growth Processes::Cell Proliferation::Cell DivisionMedical Subject Headings::Phenomena and Processes::Immune System Phenomena::Immune System Processes::Transplantation Immunology::Host vs Graft Reaction::Graft RejectionMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Organ Transplantation::Heart TransplantationMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::HomeostasisMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Phenomena and Processes::Immune System Phenomena::Immune System Processes::Immunomodulation::Immune ToleranceMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Blood Transfusion::Blood Component Transfusion::Leukocyte Transfusion::Lymphocyte TransfusionMedical Subject Headings::Diseases::Hemic and Lymphatic Diseases::Hematologic Diseases::Leukocyte Disorders::Leukopenia::LymphopeniaMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Biological::Models, ImmunologicalMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Tumor Necrosis Factor::Receptors, Tumor Necrosis Factor, Member 25Medical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Antigens, Differentiation::Antigens, CD::Receptors, Tumor Necrosis Factor, Type IIMedical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::T-Lymphocyte Subsets::T-Lymphocytes, RegulatoryMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunosuppression::Transplantation ConditioningMedical Subject Headings::Phenomena and Processes::Immune System Phenomena::Immune System Processes::Transplantation ImmunologyMedical Subject Headings::Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Tumor Necrosis Factors::Tumor Necrosis Factor-alphaMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Tissue Transplantation::Bone Marrow TransplantationMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immunologic Techniques::Immunosuppression::Lymphocyte Depletionreview article32397343open access10.3390/ijms210933471422-0067PMC7247540