Abstract:
:MicroRNAs (miRNAs) regulate many aspects of helper T cell (Th) development and function. Here we found that they are required for the suppression of interleukin-9 (IL-9) expression in Th9 cells and other Th subsets. Two highly related miRNAs (miR-15b and miR-16) that we previously found to play an important role in regulatory T (Treg) cell differentiation were capable of suppressing IL-9 expression when they were over-expressed in Th9 cells. We used these miRNAs as tools to identify novel regulators of IL-9 expression and found that they could regulate the expression of Epas1, which encodes hypoxia-inducible factor (HIF)-2α. HIF proteins regulate metabolic pathway usage that is important in determining appropriate Th differentiation. The related protein, HIF-1α enhances Th17 differentiation and inhibits Treg cell differentiation. Here we found that HIF-2α was required for IL-9 expression in Th9 cells, but its expression was not sufficient in other Th subsets. Furthermore, HIF-2α suppressed Treg cell differentiation like HIF-1α, demonstrating both similar and distinct roles of the HIF proteins in Th differentiation and adding a further dimension to their function. Ironically, even though miR-15b and miR-16 suppressed HIF-2α expression in Treg cells, inhibiting their function in Treg cells did not lead to an increase in IL-9 expression. Therefore, the physiologically relevant miRNAs that regulate IL-9 expression in Treg cells and other subsets remain unknown. Nevertheless, the analysis of miR-15b and miR-16 function led to the discovery of the importance of HIF-2α so this work demonstrated the utility of studying miRNA function to identify novel regulatory pathways in helper T-cell development.
journal_name
Immunologyjournal_title
Immunologyauthors
Singh Y,Garden OA,Lang F,Cobb BSdoi
10.1111/imm.12631subject
Has Abstractpub_date
2016-09-01 00:00:00pages
74-86issue
1eissn
0019-2805issn
1365-2567journal_volume
149pub_type
杂志文章相关文献
IMMUNOLOGY文献大全abstract::CD44, a cell adhesion molecule, exists in multiple isoforms that are generated by RNA alternative splicing. CD44 isoforms containing exon V6 (CD44 V6) have been associated with tumorigenesis and metastasis. We investigated the association between human B-cell activation and CD44 V6 isoform expression by analysing its ...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1995-09-01 00:00:00
abstract::In many species, the rejection of liver allografts is milder than that of other organs. This is especially so in the rat where, without immunosuppressive treatment, liver grafts between certain strain combinations are accepted permanently, whereas skin, heart and renal allografts undergo acute rejection. Reliable surg...
journal_title:Immunology
pub_type: 杂志文章,评审
doi:
更新日期:1985-07-01 00:00:00
abstract::Initial stages of tumour growth are not easily accessible to investigation. Therefore an experimental procedure was developed to mimic tumorigenesis as closely as possible. BALB/c mice received intraperitoneally exponentially increasing numbers of irradiated syngeneic ADJ-PC-5 plasmacytoma cells. The initial injection...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1982-11-01 00:00:00
abstract::The mechanisms of action and the nature of the co-operating cells (CC) controlling human T-lymphocyte-colony formation were investigated. Media conditioned by PHA-stimulated blood mononuclear cells (MC) were tested for their capacity to induce T-colony formation in the effluent cell population, obtained after anti (Fa...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1982-02-01 00:00:00
abstract::The fungus metabolite cyclosporin A is a small cyclic peptide acting as a novel antilymphocytic agent. It is effective following either parenteral or oral administration in mice, rats and guinea-pigs. The suppressive effect after short and prolonged treatment on plaque-forming cells, the inhibition of the secondary hu...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1977-06-01 00:00:00
abstract::Lymphocyte activation requires signal transduction mediated by reversible phosphorylation. Changing profiles of phosphorylated intermediates relate to the progressive series of transduction pathways in cells moving from G0 to G1, and thereafter through the cell cycle. We have previously shown that transient inhibition...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1992-08-01 00:00:00
abstract::Murine macrophage Fc receptor function has been studied with the membrane-impermeable sulphydryl-blocking reagent p-chloromercuribenzenesulphonic acid (PCMBSA). Antibody-dependent endocytosis of fluorescein-labelled immune complexes was studied with video intensification microscopy. PCMBSA was found to inhibit the end...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1987-02-01 00:00:00
abstract::In our efforts to identify products that might be used for active immunotherapy in human immunodeficiency virus (HIV) infection, we have studied synthetic peptides derived from the CD4 attachment site of gp120. Two peptides have emerged with particularly interesting properties. The first (B138) is linear and spans the...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1992-04-01 00:00:00
abstract::Various strains of anaerobic coryneforms and the closely related Propionibacteria have been compared in vivo with respect to their anti-tumour activity. Their effectiveness has been correlated with their serological relationship and to some extent with their ability to stimulate the lymphoreticular system. Organisms b...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1975-01-01 00:00:00
abstract::Macrophages have the potential to recognize apoptotic neutrophils and phagocytose them while the same function for monocytes is uncertain. In fact, early findings indicated that monocytes started to phagocytose neutrophils on the third day of differentiation to macrophages. Here we show, using flow cytometry and confo...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2567.2009.03087.x
更新日期:2009-09-01 00:00:00
abstract::The soluble cytoplasmic fraction of an homogenate from peritoneal rat mast cells, demonstrated a considerable amount of catalytic activity which promotes the transfer of phosphate from creatine phosphate to ADP. The plasma membrane, mitochondrial and microsomal fractions show negligible amounts of the catalyst. Enzyme...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1980-03-01 00:00:00
abstract::The role of oral-associated lymphoid tissues during induction of oral tolerance still remains elusive. Therefore, the aim was to compare T-cell activation and induction of tolerance to ovalbumin (OVA) presented through either of two routes; deposited into the oral cavity, or the stomach, thereby bypassing the oral cav...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/imm.12633
更新日期:2016-09-01 00:00:00
abstract::Macrophage (MΦ) polarization is triggered during the innate immune response to defend against microbial pathogens, but can also contribute to disease pathogenesis. In a previous study, we found that interleukin-15 (IL-15) -derived classically activated macrophages (M1 MΦ) have enhanced antimicrobial activity, whereas ...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/imm.13013
更新日期:2019-02-01 00:00:00
abstract::It has been reported previously that environmental antigens such as intestinal microflora play an important role in an age-associated increase in number of T-cell receptor gamma/delta-bearing T cells. To extend the scope of this finding, this study examined the influences of local inflammation on the accumulation and/...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1990-05-01 00:00:00
abstract::The innate immune response provides the initial defence mechanism against infection by other organisms. However, an excessive immune response will cause damage to host tissues. In an attempt to identify microRNAs (miRNAs) that regulate the innate immune response in inflammation and homeostasis, we examined the differe...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2567.2010.03374.x
更新日期:2011-05-01 00:00:00
abstract::Hyper-immunoglobulin M (IgM) syndrome (HIGM) is a rare primary immunodeficiency characterized by elevated or normal IgM and absent or markedly decreased amounts of IgG, IgA and IgE. The X-linked form (HIGM1) is the most common type and is caused by mutations in the gene for CD40L, a T-cell surface molecule required fo...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2567.2006.02520.x
更新日期:2007-04-01 00:00:00
abstract::Natural cell-mediated cytotoxicity is mediated by a family of effector cells that express cytolytic activities distinct from those generally attributed to B cells, T cells and macrophages; it includes both natural killer (NK) and natural cytotoxic (NC) activities. There is now convincing evidence to show that NC activ...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1989-08-01 00:00:00
abstract::Experiments were conducted to test the hypothesis that opsonic and non-opsonic phagocytic capacities are differentially regulated by resting and wound-derived macrophages. Furthermore, the phagocytosis of non-opsonized zymosan and beta-glucan particles was quantified to determine whether cells differentially regulate ...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1046/j.1365-2567.2001.01291.x
更新日期:2001-10-01 00:00:00
abstract::Peripheral blood lymphocytes from patients with Hashimoto's thyroiditis have been cultured for 2--3 weeks in Marbrook flasks. During this period, readily detectable amounts of thyroglobulin and microsomal antibodies were synthesized by the cells and secreted into the culture medium. Gel filtration studies indicated th...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1979-01-01 00:00:00
abstract::T. brucei infection in mice causes generalized immunosuppression with multiple changes in the cells of the lymphoid tissue. Loss of B cell responsiveness to antigens and mitogens, and the induction of suppressive T-cells and macrophages, have been previously reported (Hudson, Byner, Freeman & Terry, 1976; Corsini, Cla...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1979-02-01 00:00:00
abstract::We previously identified a cis-acting element within the 3' untranslated region of CD40 ligand messenger RNA (mRNA) that is composed of three complex binding sites and acts to increase mRNA stability in both in vitro and in vivo systems. We now demonstrate the functional consequences of the three binding sites with re...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2567.2007.02783.x
更新日期:2008-07-01 00:00:00
abstract::Factor B-like activity associated with human peripheral blood lymphocytes was first described by Halbwachs & Lachmann (1976), who employed a functional assay. In this present study, clones of B cells from patients with chronic lymphatic leukaemia (CLL) and lymphoblastoid 'Raji' cells were used. The surface of these ce...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1981-11-01 00:00:00
abstract::Animals contain an enormous load of non-pathogenic bacteria in the lower intestine, which exploit an environment with a stable temperature and abundant carbon sources. Our load of bacteria outnumbers our own cells. In order to survive with such a high number of organisms in very close proximity to host tissues the int...
journal_title:Immunology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2567.2005.02159.x
更新日期:2005-06-01 00:00:00
abstract::Paratyphoid vaccine injected between 4 days and 3 hours before injection of labelled immune complexes (125-I-labelled BGG-anti-BGG), inhibits follicular trapping of these complexes in the mouse spleen. Inhibition is maximal when paratyphoid vaccine is given 1 day before, almost no label being found in the spleen folli...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1975-06-01 00:00:00
abstract::Plasma fibronectin (FN) has been demonstrated to serve as an opsonin involved in the ingestion of foreign particles by phagocytes. This study concerns the effect of FN exposure on the respiratory burst of normal human peripheral phagocytes, using a luminol-dependent chemiluminescence (CL) assay for measurement of reac...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1988-10-01 00:00:00
abstract::Vaccination strategies that can block or limit heterosexual human immunodeficiency virus (HIV) transmissions to local and systemic tissues are the goal of much research effort. Herein, in a mouse model, we aimed to determine whether the enhancement of antibody responses through mucosal and systemic immunizations, prev...
journal_title:Immunology
pub_type: 杂志文章
doi:10.1111/j.1365-2567.2007.02702.x
更新日期:2008-03-01 00:00:00
abstract::with AgB-primed B or T cells and injected into syngeneic X-irradiated recipients. Anti-THF and anti-Eid purified by an AgB-specific T suppressor factor (TSF) affi-gel adsorbent retain their ability to specifically initiate [3H]-thymidine incorporation of AgB-primed T cells. The data indicate that both anti-THF and ant...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1982-02-01 00:00:00
abstract::Adult normal mice and those mice which had been thymectomized, X-irradiated, and reconstituted either with bone marrow cells and thymus cells (TxXBT) or with bone marrow cells along (TxXB), were given varying amounts (0.1-5 mg) of deaggregated soluble bovine serum albumin (sBSA). They were challenged 10 days later wit...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1975-05-01 00:00:00
abstract::To determine whether the availability of either B cells or T cells regulates the number and size of germinal centres observed following antigenic challenge, irradiated PVG rats were reconstituted with limiting numbers of thoracic duct B cells (with excess T cells) or with limiting numbers of thoracic duct CD4+ cells (...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00
abstract::Peripheral blood mononuclear cells (PBMC) from a patient suffering from the hyper IgE syndrome were used to generate phytohaemagglutinin (PHA)-expanded T-cell clones (all CD4+, CD8-, CD23-). A selection of the clones was tested for their ability to help IgE secretion by culturing with normal B cells in the presence of...
journal_title:Immunology
pub_type: 杂志文章
doi:
更新日期:1989-05-01 00:00:00