Distinctive Expression of Bcl-2 Factors in Regulatory T Cells Determines a Pharmacological Target to Induce Immunological Tolerance.

Abstract:

:Distinctive molecular characteristics of functionally diverse lymphocyte populations may represent novel pharmacological targets for immunotherapy. The intrinsic apoptosis pathway is differently regulated among conventional and regulatory T cells (Tregs). Targeted pharmacological modulation of this pathway with a small molecule Bcl-2/Bcl-xL inhibitor (ABT-737) caused a selective depletion of effector T cells and a relative enrichment of Tregs in vivo. Treatment with ABT-737 resulted in a tolerogenic milieu, which was exploited to alleviate graft-versus-host disease, to prevent allograft rejection in a stringent fully MHC-mismatched skin transplantation model and to induce immunological tolerance in combination with bone marrow transplantation. This concept has the potential to find various applications for immunotherapy, since it allows pharmacologic exploitation of the immunomodulatory properties of Tregs without the need for cell manipulation ex vivo.

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

Gabriel SS,Bon N,Chen J,Wekerle T,Bushell A,Fehr T,Cippà PE

doi

10.3389/fimmu.2016.00073

subject

Has Abstract

pub_date

2016-03-01 00:00:00

pages

73

issn

1664-3224

journal_volume

7

pub_type

杂志文章
  • Interplay between Transcription Factors and the Epigenome: Insight from the Role of RUNX1 in Leukemia.

    abstract::The genome has the ability to respond in a precise and co-ordinated manner to cellular signals. It achieves this through the concerted actions of transcription factors and the chromatin platform, which are targets of the signaling pathways. Our understanding of the molecular mechanisms through which transcription fact...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2015.00499

    authors: Brettingham-Moore KH,Taberlay PC,Holloway AF

    更新日期:2015-09-29 00:00:00

  • Hide and Seek: How Lyme Disease Spirochetes Overcome Complement Attack.

    abstract::Overcoming the first line of the innate immune system is a general hallmark of pathogenic microbes to avoid recognition and to enter the human host. In particular, spirochetes belonging to the Borrelia burgdorferi sensu lato complex have developed various means to counter the immune response and to successfully surviv...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2016.00385

    authors: Kraiczy P

    更新日期:2016-09-26 00:00:00

  • A Case of Adult-Onset Still's Disease Caused by a Novel Splicing Mutation in TNFAIP3 Successfully Treated With Tocilizumab.

    abstract::TNFAIP3 encodes the NF-κB regulatory protein A20. High-penetrance heterozygous mutations in TNFAIP3 cause a haploinsufficiency of A20 (HA20), inadequate inhibition of NF-κB pathway, and an early onset autoinflammatory disorder. However, the clinical phenotype of patients with HA20 varies greatly and clinical diagnoses...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.01527

    authors: Lawless D,Pathak S,Scambler TE,Ouboussad L,Anwar R,Savic S

    更新日期:2018-07-04 00:00:00

  • Aryl Hydrocarbon Receptor-Mediated Perturbations in Gene Expression during Early Stages of CD4(+) T-cell Differentiation.

    abstract::Activation of the aryl hydrocarbon receptor (AhR) by its prototypic ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mediates potent suppression of T-cell dependent immune responses. The suppressive effects of TCDD occur early during CD4(+) T-cell differentiation in the absence of effects on proliferation and have ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2012.00223

    authors: Rohlman D,Pham D,Yu Z,Steppan LB,Kerkvliet NI

    更新日期:2012-08-06 00:00:00

  • Role of Tumor-Mediated Dendritic Cell Tolerization in Immune Evasion.

    abstract::The vast majority of cancer-related deaths are due to metastasis, a process that requires evasion of the host immune system. In addition, a significant percentage of cancer patients do not benefit from our current immunotherapy arsenal due to either primary or secondary immunotherapy resistance. Importantly, select su...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.02876

    authors: DeVito NC,Plebanek MP,Theivanthiran B,Hanks BA

    更新日期:2019-12-10 00:00:00

  • Striking the Right Balance Determines TB or Not TB.

    abstract::Mycobacterium tuberculosis continues to be one of the most successful pathogens on earth. Upon inhalation of M. tuberculosis by a healthy individual, the host immune system will attempt to eliminate these pathogens using a combination of immune defense strategies. These include the recruitment of macrophages and other...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2014.00455

    authors: BoseDasgupta S,Pieters J

    更新日期:2014-10-08 00:00:00

  • Low-Dose Total Body Irradiation Can Enhance Systemic Immune Related Response Induced by Hypo-Fractionated Radiation.

    abstract::A systemic immune related response (SIME) of radiotherapy has been occasionally observed on metastatic tumors, but the clinical outcomes remain poor. Novel treatment approaches are therefore needed to improve SIME ratio. We used a combination of hypo-fractionated radiation therapy (H-RT) with low-dose total body irrad...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00317

    authors: Liu J,Zhou J,Wu M,Hu C,Yang J,Li D,Wu P,Chen Y,Chen P,Lin S,Cui Y,Fu S,Wu J

    更新日期:2019-02-27 00:00:00

  • Next-Generation Sequencing Analysis of the Human TCRγδ+ T-Cell Repertoire Reveals Shifts in Vγ- and Vδ-Usage in Memory Populations upon Aging.

    abstract::Immunological aging remodels the immune system at several levels. This has been documented in particular for the T-cell receptor (TCR)αβ+ T-cell compartment, showing reduced naive T-cell outputs and an accumulation of terminally differentiated clonally expanding effector T-cells, leading to increased proneness to auto...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00448

    authors: Kallemeijn MJ,Kavelaars FG,van der Klift MY,Wolvers-Tettero ILM,Valk PJM,van Dongen JJM,Langerak AW

    更新日期:2018-03-06 00:00:00

  • γδ T Cell-Mediated Immune Responses in Disease and Therapy.

    abstract::The role of γδ T cells in immunotherapy has gained specific importance in the recent years because of their prominent function involving directly or indirectly in the rehabilitation of the diseases. γδ T cells represent a minor population of T cells that express a distinct T cell receptor (TCR) composed of γδ chains i...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2014.00571

    authors: Latha TS,Reddy MC,Durbaka PV,Rachamallu A,Pallu R,Lomada D

    更新日期:2014-11-10 00:00:00

  • Prefusion RSV F Immunization Elicits Th2-Mediated Lung Pathology in Mice When Formulated With a Th2 (but Not a Th1/Th2-Balanced) Adjuvant Despite Complete Viral Protection.

    abstract::Respiratory syncytial virus (RSV) remains the most common cause of lower respiratory tract infections in children worldwide. Development of a vaccine has been hindered by the risk of developing enhanced respiratory disease (ERD) upon natural exposure to the virus. Generation of higher quality neutralizing antibodies w...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.01673

    authors: Eichinger KM,Kosanovich JL,Gidwani SV,Zomback A,Lipp MA,Perkins TN,Oury TD,Petrovsky N,Marshall CP,Yondola MA,Empey KM

    更新日期:2020-07-29 00:00:00

  • Age Distribution of Multiple Functionally Relevant Subsets of CD4+ T Cells in Human Blood Using a Standardized and Validated 14-Color EuroFlow Immune Monitoring Tube.

    abstract::CD4+ T cells comprise multiple functionally distinct cell populations that play a key role in immunity. Despite blood monitoring of CD4+ T-cell subsets is of potential clinical utility, no standardized and validated approaches have been proposed so far. The aim of this study was to design and validate a single 14-colo...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00166

    authors: Botafogo V,Pérez-Andres M,Jara-Acevedo M,Bárcena P,Grigore G,Hernández-Delgado A,Damasceno D,Comans S,Blanco E,Romero A,Arriba-Méndez S,Gastaca-Abasolo I,Pedreira CE,van Gaans-van den Brink JAM,Corbiere V,Mascart F,van El

    更新日期:2020-02-27 00:00:00

  • Recent Advances in Immune Cell Therapy for Glioblastoma.

    abstract::Glioblastoma (GBM) is the most malignant form of astrocytoma with short survival and a high recurrence rate and remains a global problem. Currently, surgery, chemotherapy, radiotherapy, and other comprehensive treatments are the main treatment modalities, but patients still have a poor prognosis mainly due to the infi...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.544563

    authors: Kang X,Zheng Y,Hong W,Chen X,Li H,Huang B,Huang Z,Tang H,Geng W

    更新日期:2020-10-21 00:00:00

  • Role of Macrophage Migration Inhibitory Factor in Obesity, Insulin Resistance, Type 2 Diabetes, and Associated Hepatic Co-Morbidities: A Comprehensive Review of Human and Rodent Studies.

    abstract::Obesity is associated with a chronic low-grade inflammatory state that drives the -development of obesity-related co-morbidities such as insulin resistance/type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease. This metabolic inflammation is thought to originate in the adipose tissue, ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2015.00308

    authors: Morrison MC,Kleemann R

    更新日期:2015-06-15 00:00:00

  • Epigenetic Regulation of Interleukin 6 by Histone Acetylation in Macrophages and Its Role in Paraquat-Induced Pulmonary Fibrosis.

    abstract::Overexpression of interleukin 6 (IL-6) has been proposed to contribute to pulmonary fibrosis and other fibrotic diseases. However, the regulatory mechanisms and the role of IL-6 in fibrosis remain poorly understood. Epigenetics refers to alterations of gene expression without changes in the DNA sequence. Alternation o...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2016.00696

    authors: Hu L,Yu Y,Huang H,Fan H,Hu L,Yin C,Li K,Fulton DJ,Chen F

    更新日期:2017-01-30 00:00:00

  • Severe Heterotopic Ossification in the Skeletal Muscle and Endothelial Cells Recruitment to Chondrogenesis Are Enhanced by Monocyte/Macrophage Depletion.

    abstract::Altered macrophage infiltration upon tissue damage results in inadequate healing due to inappropriate remodeling and stem cell recruitment and differentiation. We investigated in vivo whether cells of endothelial origin phenotypically change upon heterotopic ossification induction and whether infiltration of innate im...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.01640

    authors: Tirone M,Giovenzana A,Vallone A,Zordan P,Sormani M,Nicolosi PA,Meneveri R,Gigliotti CR,Spinelli AE,Bocciardi R,Ravazzolo R,Cifola I,Brunelli S

    更新日期:2019-07-19 00:00:00

  • TCR Convergence in Individuals Treated With Immune Checkpoint Inhibition for Cancer.

    abstract::Tumor antigen-driven selection may expand T cells having T cell receptors (TCRs) of shared antigen specificity but different amino acid or nucleotide sequence in a process known as TCR convergence. Substitution sequencing errors introduced by TCRβ (TCRB) repertoire sequencing may create artifacts resembling TCR conver...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.02985

    authors: Looney TJ,Topacio-Hall D,Lowman G,Conroy J,Morrison C,Oh D,Fong L,Zhang L

    更新日期:2020-01-09 00:00:00

  • The Immune Epitope Database and Analysis Resource in Epitope Discovery and Synthetic Vaccine Design.

    abstract::The task of epitope discovery and vaccine design is increasingly reliant on bioinformatics analytic tools and access to depositories of curated data relevant to immune reactions and specific pathogens. The Immune Epitope Database and Analysis Resource (IEDB) was indeed created to assist biomedical researchers in the d...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.00278

    authors: Fleri W,Paul S,Dhanda SK,Mahajan S,Xu X,Peters B,Sette A

    更新日期:2017-03-14 00:00:00

  • Revisiting mouse peritoneal macrophages: heterogeneity, development, and function.

    abstract::Tissue macrophages play a crucial role in the maintenance of tissue homeostasis and also contribute to inflammatory and reparatory responses during pathogenic infection and tissue injury. The high heterogeneity of these macrophages is consistent with their adaptation to distinct tissue environments and specialization ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2015.00225

    authors: Cassado Ados A,D'Império Lima MR,Bortoluci KR

    更新日期:2015-05-19 00:00:00

  • Microbiome-Derived Lipopolysaccharide Enriched in the Perinuclear Region of Alzheimer's Disease Brain.

    abstract::Abundant clinical, epidemiological, imaging, genetic, molecular, and pathophysiological data together indicate that there occur an unusual inflammatory reaction and a disruption of the innate-immune signaling system in Alzheimer's disease (AD) brain. Despite many years of intense study, the origin and molecular mechan...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01064

    authors: Zhao Y,Cong L,Jaber V,Lukiw WJ

    更新日期:2017-09-04 00:00:00

  • Human Bone Marrow-Derived Myeloid Dendritic Cells Show an Immature Transcriptional and Functional Profile Compared to Their Peripheral Blood Counterparts and Separate from Slan+ Non-Classical Monocytes.

    abstract::The human bone marrow (BM) gives rise to all distinct blood cell lineages, including CD1c+ (cDC2) and CD141+ (cDC1) myeloid dendritic cells (DC) and monocytes. These cell subsets are also present in peripheral blood (PB) and lymphoid tissues. However, the difference between the BM and PB compartment in terms of differ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.01619

    authors: van Leeuwen-Kerkhoff N,Lundberg K,Westers TM,Kordasti S,Bontkes HJ,Lindstedt M,de Gruijl TD,van de Loosdrecht AA

    更新日期:2018-07-16 00:00:00

  • Roles of Autophagy and Autophagy-Related Proteins in Antifungal Immunity.

    abstract::Autophagy was initially characterized as a process to digest cellular components, including damaged cell organelles or unused proteins. However, later studies showed that autophagy plays an important role to protect hosts from microbial infections. Accumulating evidences showed the contribution of autophagy itself and...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2016.00047

    authors: Kanayama M,Shinohara ML

    更新日期:2016-02-18 00:00:00

  • Allies or Enemies-The Multifaceted Role of Myeloid Cells in the Tumor Microenvironment.

    abstract::For decades, cancer was considered a disease driven by genetic mutations in tumor cells, therefore afflicting a single cell type. This simplified view was slowly replaced by the understanding that interactions between malignant cells and neighboring stromal and immune cells-the tumor microenvironment (TME)-profoundly ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.02746

    authors: Haas L,Obenauf AC

    更新日期:2019-11-28 00:00:00

  • Hypomorphic Mutations in the BCR Signalosome Lead to Selective Immunoglobulin M Deficiency and Impaired B-cell Homeostasis.

    abstract::B cell activation via the B cell receptor (BCR) signalosome involves participation of signaling molecules such as BTK and BLNK. Genetic defects in these molecules are known to impair B cell differentiation and subsequently lead to agammaglobulinemia. Here we identified novel mutations in BTK and BLNK in two unrelated ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.02984

    authors: Geier CB,Sauerwein KMT,Leiss-Piller A,Zmek I,Fischer MB,Eibl MM,Wolf HM

    更新日期:2018-12-18 00:00:00

  • Immunological Aspect of Radiation-Induced Pneumonitis, Current Treatment Strategies, and Future Prospects.

    abstract::Delivery of high doses of radiation to thoracic region, particularly with non-small cell lung cancer patients, becomes difficult due to subsequent complications arising in the lungs of the patient. Radiation-induced pneumonitis is an early event evident in most radiation exposed patients observed within 2-4 months of ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.00506

    authors: Kainthola A,Haritwal T,Tiwari M,Gupta N,Parvez S,Tiwari M,Prakash H,Agrawala PK

    更新日期:2017-05-02 00:00:00

  • The Length of N-Glycans of Recombinant H5N1 Hemagglutinin Influences the Oligomerization and Immunogenicity of Vaccine Antigen.

    abstract::Hemagglutinin glycoprotein (HA) is a principle influenza vaccine antigen. Recombinant HA-based vaccines become a potential alternative for traditional approach. Complexity and variation of HA N-glycosylation are considered as the important factors for the vaccine design. The number and location of glycan moieties in t...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00444

    authors: Macioła AK,Pietrzak MA,Kosson P,Czarnocki-Cieciura M,Śmietanka K,Minta Z,Kopera E

    更新日期:2017-04-20 00:00:00

  • Immunological Aspects of Approved MS Therapeutics.

    abstract::Multiple sclerosis (MS) is the most common neurological immune-mediated disease leading to disability in young adults. The outcome of the disease is unpredictable, and over time, neurological disabilities accumulate. Interferon beta-1b was the first drug to be approved in the 1990s for relapsing-remitting MS to modula...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.01564

    authors: Rommer PS,Milo R,Han MH,Satyanarayan S,Sellner J,Hauer L,Illes Z,Warnke C,Laurent S,Weber MS,Zhang Y,Stuve O

    更新日期:2019-07-11 00:00:00

  • Immunoglobulin A Isotype of Antiphospholipid Antibodies Does Not Provide Added Value for the Diagnosis of Antiphospholipid Syndrome in a Chinese Population.

    abstract:Objective:Antiphospholipid syndrome (APS) is characterized by the presence of anti-phospholipid (aPL) antibodies. However, the relationship between the immunoglobulin (Ig) A isotype of aPL positivity and its clinical utility in APS diagnosis is controversial. Presently, we determine the clinical utility of IgA-aPL from...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.568503

    authors: Hu C,Li X,Zhao J,Wang Q,Li M,Tian X,Zeng X

    更新日期:2020-10-05 00:00:00

  • PD-L1/PD-1 Pattern of Expression Within the Bone Marrow Immune Microenvironment in Smoldering Myeloma and Active Multiple Myeloma Patients.

    abstract:Background:The PD-1/PD-L1 axis has recently emerged as an immune checkpoint that controls antitumor immune responses also in hematological malignancies. However, the use of anti-PD-L1/PD-1 antibodies in multiple myeloma (MM) patients still remains debated, at least in part because of discordant literature data on PD-L1...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.613007

    authors: Costa F,Vescovini R,Marchica V,Storti P,Notarfranchi L,Dalla Palma B,Toscani D,Burroughs-Garcia J,Catarozzo MT,Sammarelli G,Giuliani N

    更新日期:2021-01-08 00:00:00

  • Rare Functional Variants in Complement Genes and Anti-FH Autoantibodies-Associated aHUS.

    abstract::Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia and renal failure. It is caused by genetic or acquired defects of the complement alternative pathway. Factor H autoantibodies (anti-FHs) have been reported in 10% of aHUS patients and are as...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00853

    authors: Valoti E,Alberti M,Iatropoulos P,Piras R,Mele C,Breno M,Cremaschi A,Bresin E,Donadelli R,Alizzi S,Amoroso A,Benigni A,Remuzzi G,Noris M

    更新日期:2019-05-01 00:00:00

  • Volcanic Ash Activates the NLRP3 Inflammasome in Murine and Human Macrophages.

    abstract::Volcanic ash is a heterogeneous mineral dust that is typically composed of a mixture of amorphous (glass) and crystalline (mineral) fragments. It commonly contains an abundance of the crystalline silica (SiO2) polymorph cristobalite. Inhalation of crystalline silica can induce inflammation by stimulating the NLRP3 inf...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.02000

    authors: Damby DE,Horwell CJ,Baxter PJ,Kueppers U,Schnurr M,Dingwell DB,Duewell P

    更新日期:2018-01-22 00:00:00