Abstract:
:Transfer of recipient regulatory T cells (Tregs) induces mixed chimerism and tolerance in an irradiation-free bone marrow (BM) transplantation (BMT) model involving short-course co-stimulation blockade and mTOR inhibition. Boosting endogenous Tregs pharmacologically in vivo would be an attractive alternative avoiding the current limitations of performing adoptive cell therapy in the routine clinical setting. Interleukin-6 (IL-6) potently inhibits Treg differentiation and its blockade was shown to increase Treg numbers in vivo. Therefore, we investigated whether IL-6 blockade can replace adoptive Treg transfer in irradiation-free allogeneic BMT. Treatment with anti-IL-6 instead of Treg transfer led to multi-lineage chimerism (persisting for ~12 weeks) in recipients of fully mismatched BM and significantly prolonged donor skin (MST 58 days) and heart (MST > 100 days) graft survival. Endogenous Foxp3+ Tregs expanded in anti-IL-6-treated BMT recipients, while dendritic cell (DC) activation and memory CD8+ T cell development were inhibited. Adding anti-IL-17 to anti-IL-6 treatment increased Treg frequencies, but did not further prolong donor skin graft survival significantly. These results demonstrate that IL-6 blockade promotes BM engraftment and donor graft survival in non-irradiated recipients and might provide an alternative to Treg cell therapy in the clinical setting.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Granofszky N,Farkas AM,Muckenhuber M,Mahr B,Unger L,Maschke S,Pilat N,Holly R,Wiletel M,Regele H,Wekerle Tdoi
10.3389/fimmu.2017.00821subject
Has Abstractpub_date
2017-07-19 00:00:00pages
821issn
1664-3224journal_volume
8pub_type
杂志文章abstract::The main role of the human immune system is to eliminate cells presenting foreign antigens and abnormal patterns, while maintaining self-tolerance. However, when facing highly variable pathogens or antigens very similar to self-antigens, this system can fail in completely eliminating the anomalies, leading to the esta...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.01350
更新日期:2020-06-30 00:00:00
abstract::HIV-1 is transcriptionally active in activated T helper (Th)-cells and inactive in naive or resting memory Th-cells. Ets-2 is a preinduction transcriptional repressor of the IL-2 gene in naive Th-cells and a candidate transcriptional repressor of HIV-1 in the same cells, because the -279 to -250 upstream region of HIV...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.01924
更新日期:2018-01-04 00:00:00
abstract::Inflammatory bowel disease (IBD) is a chronic and relapsing intestinal inflammatory condition with no effective treatment. Probiotics have gained wide attention because of their outstanding advantages in intestinal health issues. In previous studies, a novel soluble protein, HM0539, which is derived from Lactobacillus...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.551449
更新日期:2020-10-05 00:00:00
abstract:Introduction:The broccoli isothiocyanate sulforaphane was shown to inhibit inflammation and tumor progression, also in pancreatic cancer, while its effect on tumor immunity is poorly understood. We investigated the immunoregulatory effect of sulforaphane on human dendritic cells alone and in presence of pancreatic tumo...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.589818
更新日期:2020-10-30 00:00:00
abstract::The heat-labile toxins (LT) produced by enterotoxigenic Escherichia coli display adjuvant effects to coadministered antigens, leading to enhanced production of serum antibodies. Despite extensive knowledge of the adjuvant properties of LT derivatives, including in vitro-generated non-toxic mutant forms, little is know...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.01175
更新日期:2017-09-25 00:00:00
abstract::Antibodies can rapidly evolve in specific response to antigens. Affinity maturation drives this evolution through cycles of mutation and selection leading to enhanced antibody specificity and affinity. Elucidating the biophysical mechanisms that underlie affinity maturation is fundamental to understanding B-cell immun...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00413
更新日期:2018-03-02 00:00:00
abstract::Dyslipidemia is a central component of atherosclerosis and metabolic syndrome linked to chronic inflammation and immune dysfunction. Previously, we showed that hypercholesterolemic apolipoprotein E knock out (apoE-/-) mice exhibit systemic effects including skin inflammation and hypertrophic lymph nodes (LNs). However...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00575
更新日期:2019-03-27 00:00:00
abstract::NK cells are capable of an array of functions that range widely from their classic anti-tumor and anti-viral cytotoxic effector functions, to their critical regulatory roles in controlling inflammatory immune responses and promoting tissue growth. However, the mechanisms that polarize NK cells to these distinct and op...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.01414
更新日期:2019-06-19 00:00:00
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
更新日期:2017-09-04 00:00:00
abstract::Advances in the understanding of leishmaniasis progression indicate that cellular interactions more complex than the Th1/Th2 paradigm define the course of infection. Th17 cells are a crucial modulator of adaptive immunity against Leishmania parasites acting mainly on neutrophil recruitment and playing a dual role at t...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.01437
更新日期:2017-10-30 00:00:00
abstract::The induction of Th2 responses is thought to be multifactorial, and emerge from specific pathways distinct from those associated with antagonistic antibacterial or antiviral Th1 responses. Here, we show that the recognition of non-viable Nippostrongylus brasiliensis (Nb) in the skin induces a strong recruitment of mon...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.01575
更新日期:2017-11-16 00:00:00
abstract::The developmental origin of allergic diseases has been suggested, but the molecular basis remains enigmatic. Exposure to environmental factors, such as di-(2-ethylhexyl) phthalate (DEHP; a common plasticizer), is suggested to be associated with increased childhood allergic asthma, but the causal relationship and its u...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.603831
更新日期:2020-12-23 00:00:00
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
更新日期:2019-11-28 00:00:00
abstract::The glycans on the plasma membrane of cells manifest as the glycocalyx, which serves as an information-rich frontier that is directly in contact with its immediate milieu. The glycoconjugates (GCs) that adorn most of the mammalian cells are also abundant in gametes, especially the spermatozoa where they perform unique...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.01928
更新日期:2020-08-28 00:00:00
abstract::Natural killer (NK) cells are the major innate effectors primed to eliminate virus-infected and tumor or neoplastic cells. Recent studies also suggest nuances in phenotypic and functional characteristics among NK cell subsets may further permit execution of regulatory and adaptive roles. Animal models, particularly no...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.01124
更新日期:2019-05-22 00:00:00
abstract::Disease suppressive T cell regulation may depend on cognate interactions of regulatory T cells with self-antigens that are abundantly expressed in the inflamed tissues. Heat shock proteins (HSPs) are by their nature upregulated in stressed cells and therefore abundantly present as potential targets for such regulation...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.01690
更新日期:2017-11-30 00:00:00
abstract::Soluble CD83 (sCD83) is the extracellular domain of the membrane-bound CD83 molecule, and known for its immunoregulatory functions. Whether and how sCD83 participates in the pathogenesis of uveitis, a serious inflammatory disease of the eye that can cause visual disability and blindness, is unknown. By flow cytometry ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01567
更新日期:2018-07-09 00:00:00
abstract::Regulatory B (Breg) cells represent a population of suppressor B cells that participate in immunomodulatory processes and inhibition of excessive inflammation. The regulatory function of Breg cells have been demonstrated in mice and human with inflammatory diseases, cancer, after transplantation, and particularly in a...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.01884
更新日期:2020-08-20 00:00:00
abstract::Tumor necrosis factor-α inhibitors (TNFis) have revolutionized the management of rheumatoid arthritis (RA), however despite considerable progress, only a small proportion of patients maintain long-term clinical response. Selection of, and switching between, biologics is mainly empirical, experiential, and not evidence...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00589
更新日期:2020-04-07 00:00:00
abstract::Visceral leishmaniasis (VL)-related mortality and morbidity imposes a great deal of health concern across the globe. The existing anti-leishmanial drug regimen generally fails to eliminate newly emerging resistant isolates of this dreadful parasite. In such circumstances, the development of a prophylactic strategy to ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00817
更新日期:2020-06-02 00:00:00
abstract::Iron is an essential micronutrient for most living species. In mammals, hemoglobin (Hb) stores more than two thirds of the body's iron content. In the bloodstream, haptoglobin (Hp) and hemopexin (Hpx) sequester free Hb or heme. Pathogenic microorganisms usually acquire iron from their hosts and have evolved complex sy...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02086
更新日期:2018-09-11 00:00:00
abstract::Our aim was to analyze the relationship between plasma inflammatory biomarkers and CD4+ T-cells evolution in human immunodeficiency virus (HIV) elite controllers (HIV-ECs) with a suppressed viremia. We carried out a retrospective study in 30 HIV-ECs classified into two groups: those showing no significant loss of CD4+...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01399
更新日期:2018-06-18 00:00:00
abstract::Common Variable Immunodeficiency (CVID) is characterized by impaired antibody production and poor terminal differentiation of the B cell compartment, yet its pathogenesis is still poorly understood. We first reported the occurrence of epigenetic alterations in CVID by high-throughput methylation analysis in CVID-disco...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00878
更新日期:2019-04-24 00:00:00
abstract::Pregnancy comprises a unique immunological condition, to allow fetal development and to protect the host from pathogenic infections. Viral infections during pregnancy can disrupt immunological tolerance and may generate deleterious effects on the fetus. Despite these possible links between pregnancy and infection-indu...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.01672
更新日期:2020-07-07 00:00:00
abstract::Unlike mice and humans, porcine γδ T cells represent a prominent subset of T cells in blood and secondary lymphatic organs. GATA-3, T-bet and Eomesodermin (Eomes) are transcription factors with crucial functions in T-cell development and functional differentiation, but their expression has not been investigated in por...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00396
更新日期:2019-03-11 00:00:00
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
更新日期:2017-05-02 00:00:00
abstract::[This corrects the article DOI: 10.3389/fimmu.2020.562282.]. ...
journal_title:Frontiers in immunology
pub_type: 已发布勘误
doi:10.3389/fimmu.2020.625157
更新日期:2020-12-16 00:00:00
abstract::Immunoglobulin superfamily member (IgSF) proteins play a significant role in regulating immune responses with surface expression on all immune cell subsets, making the IgSF an attractive family of proteins for therapeutic targeting in human diseases. We have developed a directed evolution platform capable of engineeri...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.03086
更新日期:2020-01-21 00:00:00
abstract::Diet composition may affect the onset and progression of chronic degenerative diseases, including cancer, whose pathogenesis relies on inflammatory processes. Growing evidence indicates that diet and its components critically contribute to human health, affecting the immune system, secretion of adipokines, and metabol...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2016.00486
更新日期:2016-11-15 00:00:00
abstract::The inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory disorders of the intestine. The prevalence in the United States is greater than 200 cases per 100,000, with the total number of IBD patients between 1 and 1.5 million. CD may affect all parts of ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2012.00107
更新日期:2012-05-08 00:00:00