Abstract:
:Fanconi anemia (FA) is a genetic disorder associated with bone marrow (BM) failure and leukemia. Recent studies demonstrate variable immune defects in FA. However, the cause for FA immunodeficiency is unknown. Here we report that deletion of Fanca or Fancd2 dysregulates the suppressive activity of regulatory T cells (Tregs), shown functionally as exacerbation of graft-vs-host disease (GVHD) in mice. Recipient mice of Fanca(-/-) or Fancd2(-/-) BM chimeras exhibited severe acute GVHD after allogeneic BM transplantation (BMT). T cells from Fanca(-/-) or Fancd2(-/-) mice induced higher GVHD lethality than those from wild-type (WT) littermates. FA Tregs possessed lower proliferative suppression potential compared with WT Tregs, as demonstrated by in vitro proliferation assay and BMT. Analysis of CD25(+)Foxp3(+) Tregs indicated that loss of Fanca or Fancd2 dysregulated Foxp3 target gene expression. Additionally, CD25(+)Foxp3(+) Tregs of Fanca(-/-) or Fancd2(-/-) mice were less efficient in suppressing the production of GVHD-associated inflammatory cytokines. Consistently, aberrant NF-κB activity was observed in infiltrated T cells from FA GVHD mice. Conditional deletion of p65 in FA Tregs decreased GVHD mortality. Our study uncovers an essential role for FA proteins in maintaining Treg homeostasis, possibly explaining, at least in part, the immune deficiency reported in some FA patients.
journal_name
Bloodjournal_title
Bloodauthors
Du W,Erden O,Wilson A,Sipple JM,Schick J,Mehta P,Myers KC,Steinbrecher KA,Davies SM,Pang Qdoi
10.1182/blood-2013-09-528018subject
Has Abstractpub_date
2014-03-20 00:00:00pages
1938-47issue
12eissn
0006-4971issn
1528-0020pii
blood-2013-09-528018journal_volume
123pub_type
杂志文章相关文献
BLOOD文献大全abstract::The mechanisms by which tumors metastasize to sentinel and distant lymph nodes, and beyond, are poorly understood. We developed transgenic mice that overexpress vascular endothelial growth factor-C (VEGF-C) and green fluorescent protein specifically in the skin and studied the effects of chemically-induced skin carcin...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-05-021758
更新日期:2007-02-01 00:00:00
abstract::In this issue of Blood, Rowley et al report that noncoding RNAs precisely regulate the messenger RNA (mRNA) profile in platelets. Interfering in this process using genetically engineered mice affects hemostatic and thrombotic functions of platelets. ...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2016-01-694893
更新日期:2016-04-07 00:00:00
abstract::The molecular determinants regulating the specification of human embryonic stem cells (hESCs) into hematopoietic cells remain elusive. HOXA9 plays a relevant role in leukemogenesis and hematopoiesis. It is highly expressed in hematopoietic stem and progenitor cells (HSPCs) and is downregulated upon differentiation. Ho...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-03-558825
更新日期:2014-11-13 00:00:00
abstract::The proteolytic cleavage and subsequent inactivation of recombinant human factor VIII (rhFVIII) and human factor VIIIa (rhFVIIIa) by recombinant human activated protein C (rAPC) was analyzed in the presence and absence of human protein S and human factor V (FV). Membrane-bound rhFVIIIa spontaneously looses most of its...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-06-01 00:00:00
abstract::Rauscher murine erythroleukemia cells, grown continuously in vitro, undergo erythroid differentiation in response to the hormone erythropoietin. Therefore, they serve as an important model system with which to examine critical biochemical aspects of this developmental process. Intact, uninduced Rauscher cells possess ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1984-07-01 00:00:00
abstract::One of the most serious complications of successful treatments for Hodgkin's disease is an increased incidence of acute nonlymphocytic leukemia (ANLL) and other malignancies. A retrospective analysis carried out on 1032 consecutive patients with Hodgkin's disease admitted to our Institute between 1965 and 1978 and tre...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1982-03-01 00:00:00
abstract::Although recent advances have enabled hematopoietic stem cells (HSCs) to be enriched to near purity, more information about their characteristics will improve our understanding of their development and stage-related functions. Here, using microarray technology, we identified endothelial cell-selective adhesion molecul...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-07-167106
更新日期:2009-03-26 00:00:00
abstract::We used synthetic peptides to the extracellular loops (ECLs) of CCR5 to examine inhibitory effects on HIV infection/fusion with primary leukocytes and cells expressing recombinant CCR5. We show for the first time that peptides derived from the first, second, or third ECL caused dose-dependent inhibition of fusion and ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-08-2669
更新日期:2004-02-15 00:00:00
abstract::Although the mechanisms by which all-trans-retinoic acid (RA) regulates gene transcription are well understood, very little is known on the signaling events regulating RA-dependent initiation of mRNA translation. We examined whether the mammalian target of rapamycin (mTOR)/p70 S6 kinase pathway is activated by RA. RA ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-06-2078
更新日期:2005-02-15 00:00:00
abstract::Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematologic disorder with multiple and varied clinical manifestations. The biochemical defect in PNH resides in the incomplete enzymatic assembly of glycosylphosphatidylinositol (GPI) anchors used for surface protein attachment. In all patients tested thu...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-05-01 00:00:00
abstract::Toll-like receptors (TLRs) are able to interact with pathogen-derived products and their signals induce the coordinated activation of innate and adaptive immune mechanisms. Dendritic cells (DCs) play a central role in these events. As the different TLRs are able to trigger MyD88/TRIF-dependent and -independent signali...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-10-4015
更新日期:2006-07-15 00:00:00
abstract::Asparaginase is an enzyme used in the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma in children. It has minimal bone marrow toxicity. Its major side effects are anaphylaxis, pancreatitis, diabetes, coagulation abnormalities, and thrombosis, especially intracranial. It is derived from 2 different...
journal_title:Blood
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1182/blood.v99.8.2734
更新日期:2002-04-15 00:00:00
abstract::The interleukin-4 receptor (IL-4R) is expressed as a 140-Kd membrane glycoprotein that binds IL-4 with high affinity. Recently, cDNA clones for the murine IL-4R have been isolated. One clone encodes an integral membrane protein, while another encodes a protein in which translation is terminated before the transmembran...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-06-01 00:00:00
abstract::Protective protein/cathepsin A (PPCA), a lysosomal carboxypeptidase, is deficient in the neurodegenerative lysosomal disorder galactosialidosis (GS). PPCA(-/-) mice display a disease course similar to that of severe human GS, resulting in nephropathy, ataxia, and premature death. Bone marrow transplantation (BMT) in m...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.9.3169
更新日期:2002-05-01 00:00:00
abstract::In a randomized multicenter study the influence of hydroxyurea versus busulfan on the duration of the chronic phase and on survival of chronic myelogenous leukemia (CML) was determined. In addition cross resistance and adverse reactions of the drugs were analyzed. From July 1983 to January 1991, 441 CML patients were ...
journal_title:Blood
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1993-07-15 00:00:00
abstract::The transmembrane 4 superfamily (TM4SF) has come into prominence for its association with a wide range of cell surface molecules, especially integrins. We report that TM4SF molecules CD9, CD63, and CD81 are physically associated with c-kit receptor tyrosine kinase in the human factor-dependent myeloid cell line, MO7e....
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.12.4413
更新日期:2002-06-15 00:00:00
abstract::We analyzed the effect of aspirin, salicylate, and other nonsteroidal antiinflammatory drugs (NSAIDs) on the viability of B-chronic lymphocytic leukemia (B-CLL) cells. Aspirin induced a decrease in cell viability in a dose- and time-dependent manner. The mean IC50 for cells from 5 patients was 5.9 +/- 1.13 mmol/L (ran...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-08-15 00:00:00
abstract::The reactivation of human cytomegalovirus (HCMV) poses a serious health threat to immune compromised individuals. As a treatment strategy, dendritic cell (DC) vaccination trials are ongoing. Recent work suggests that BDCA-3(+) (CD141(+)) subset DCs may be particularly effective in DC vaccination trials. BDCA-3(+) DCs ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-06-434498
更新日期:2012-12-20 00:00:00
abstract::Human hematopoietic colony-forming cells (CFC) express the CD34 antigen (CD34+) as well as differentiation antigens such as CD33 and HLA-DR. CD34+ cells that do not express these latter differentiation antigens have been shown to contain few CFC in direct culture, but generate increasing numbers of CFC when cultured o...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-06-01 00:00:00
abstract::Cloned T9-C2 glioma cells transfected with membrane macrophage colony-stimulating factor (mM-CSF) never formed subcutaneous tumors when implanted into Fischer rats, whereas control T9 cells did. The T9-C2 cells were completely killed within 1 day through a mechanism that resembled paraptosis. Vacuolization of the T9-C...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-01-0174
更新日期:2002-08-15 00:00:00
abstract::Evidence has been provided recently that shows that high concentrations of cytokines can fulfill functions previously attributed to stromal cells, such as promote the survival of, and led to a net increase in human primitive progenitors initiating long-term cultures in vitro (LTC-IC) or engrafting NOD-SCID (nonobese d...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-07-15 00:00:00
abstract::Serotonin (5-hydroxytryptamine, or 5-HT), released from activated platelets, not only accelerates aggregation of platelets but also is known to promote mitosis, migration, and contraction of vascular smooth muscle cells (VSMCs). These effects are considered to contribute to thrombus formation and atherosclerosis. The ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v97.6.1697
更新日期:2001-03-15 00:00:00
abstract::At the intersection between children and older adults, the care of adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) poses unique challenges and issues beyond those faced by other age groups. Although the survival of AYA patients is inferior to younger children, growing evidence suggest...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2014-11-551481
更新日期:2015-06-11 00:00:00
abstract::Increasing evidence indicates that the gut microbiota is closely associated with acute graft-versus-host disease (aGVHD) in stem cell transplantation (SCT). Fecal microbiota transplantation (FMT) could represent an alternative treatment option for aGVHD. However, FMT for SCT patients carries a potential risk of infect...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2016-05-717652
更新日期:2016-10-20 00:00:00
abstract::The relationship between platelet density and platelet age appears to vary between species with relatively few labeling studies in humans reported. In this study, irreversible monoamine oxidase (MAO) inhibitors were used to biochemically label the circulating platelet population in 15 humans. Platelet samples were the...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1989-04-01 00:00:00
abstract::In systemic light-chain amyloidosis, λ light chains produced by clonal plasma cells cause organ damage and early death. In pursuit of novel therapy, we developed 1 pool of short interfering RNA (siRNA) targeting the constant region of λ light chains that substantially and promptly reduces λ-light-chain production and ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-10-535187
更新日期:2014-05-29 00:00:00
abstract::Infections during granulocytopenia are major complications of autologous bone marrow transplantation (ABMT). Since recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) has proved to accelerate bone marrow recovery after cytostatic chemotherapy, we studied its effects on hematopoietic regenera...
journal_title:Blood
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1992-11-01 00:00:00
abstract::Contraction of blood clots is necessary for hemostasis and wound healing and to restore flow past obstructive thrombi, but little is known about the structure of contracted clots or the role of erythrocytes in contraction. We found that contracted blood clots develop a remarkable structure, with a meshwork of fibrin a...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-08-523860
更新日期:2014-03-06 00:00:00
abstract::Although the chromosomal localization (9q34) of the gene encoding the human form of ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13) and its exclusive expression in the liver have been established, the cells that produce this enzyme are yet to be determined. We investigated the ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-01-0152
更新日期:2005-08-01 00:00:00
abstract::Recent studies have established that during embryonic development, hematopoietic progenitors and stem cells are generated from hemogenic endothelium precursors through a process termed endothelial to hematopoietic transition (EHT). The transcription factor RUNX1 is essential for this process, but its main downstream e...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-10-386094
更新日期:2012-07-12 00:00:00