Biomedical subjects

H A Young

Publications and source records attributed to H A Young.

At least 19 recordsLinked to original sources

PubMed1999

IL-18 is a potent coinducer of IL-13 in NK and T cells: a new potential role for IL-18 in modulating the immune response.

IL-13 and IL-4 have similar biological activities and are characteristic of cytokines expressed by Th2 cells. In contrast, IL-12 and IL-18 have been shown to be strong cofactors for Th1 cell development. In this study, we found strong induction of IL-13 mRNA and protein by IL-2 + IL-18 in NK and T cells. In contrast, IL-12 did not enhance the IL-13 production induced by IL-2 alone. Moreover, IL-13 mRNA and protein expression induced by IL-2 + IL-18 in purified NK and T cells obtained from IFN-gamma knockout (-/-) mice were greater than seen in purified cells from normal controls. In contrast, IL-10 production induced by IL-2 and/or IL-12 was not significantly different in IFN-gamma (-/-) mice and normal controls. These results suggest IL-13 expression induced by IL-2 + IL-18 may be regulated by IFN-gamma in vivo, while IL-10 expression may be IFN-gamma-independent. Thus, depending upon the cell type, IL-18 may act as a strong coinducer of Th1 or Th2 cytokines. Our findings suggest that IL-12 and IL-18 have different roles in the regulation of gene expression in NK and T cells.

Adjuvants, Immunologic↗

PubMed1999

Role of a STAT binding site in the regulation of the human perforin promoter.

The pore-forming protein perforin is preferentially expressed in NK and cytotoxic T cells. To investigate the molecular regulation of human perforin gene transcription, the activity of the human perforin promoter was analyzed in human NK and T cell lines using various promoter fragments linked to a luciferase reporter gene. A core promoter was identified within 55 bp upstream of the transcription start site. This promoter region contains a guanine/cytosine box and has basal activity in YT, Kit225-k6, and Jurkat cells. A strong enhancer activity was identified between positions -1136 and -1076, a region that includes a STAT-like element. This enhancer region was active in YT cells, which have constitutive perforin expression and activated STAT3 protein, but not in Kit225-k6 or Jurkat cells, which do not have constitutive perforin expression. Mutation of the STAT binding site resulted in a dramatic down-regulation of promoter activity. Electrophoretic mobility shift assays, using a probe containing the STAT element of the perforin promoter, indicated that this element can bind STAT3 from YT cells. Moreover, the STAT element was shown to bind STAT5a/b induced by IL-2 as well as STAT1alpha induced by IL-6 in human NK cells. Together, these results suggest that STAT proteins play a key role in perforin gene transcription and provide a model by which cytokines can regulate perforin gene expression.

Binding Sites↗

PubMed1999

IL-13 production by NK cells: IL-13-producing NK and T cells are present in vivo in the absence of IFN-gamma.

In this study, we demonstrate that human NK cells, human NK clones, the human NK cell line (NK3.3), and a population of murine NK cells can produce the type 2 cytokine IL-13 in response to IL-2 or phorbol myristate acetate plus ionomycin. IL-2 rapidly induced new IL-13 mRNA and protein synthesis in the NK3.3 cell line. Six of 12 human NK clones tested produced IL-13 protein in response to IL-2 or phorbol myristate acetate and ionomycin. Intracellular analysis revealed that approximately 2% of human peripheral NK cells produced IL-13 protein in response to IL-2. Isolated NK cells from SCID and RAG-2 knockout (-/-) mice that lack T and B cells as well as normal mice also can produce IL-13 mRNA and protein in response to IL-2. We hypothesized that in the absence of IFN-gamma, IL-13-producing NK cells may predominate in vivo. Utilizing IFN-gamma knockout (-/-) mice as a model system, IL-2-activated liver NK and T cells expressed 10-fold more IL-13 and IL-5 mRNA and protein than normal controls following IL-2 treatment in vitro. These results suggest that in the absence of IFN-gamma, an IL-13- and IL-5-producing NK and T cells predominate in vivo. The existence of this cell type has important implications in innate immunity given that the balance between IFN-gamma and IL-13/IL-5-producing NK cells may influence the early development of a cell-mediated or humoral immune response.

Animals↗

PubMed1999

Divergent effects of dithiocarbamates on AP-1-containing and AP-1-less NFAT sites.

Changes in the redox status of cells affect NF-kappaB and activator protein (AP)-1 nuclear expression and activity. In particular, antioxidants decrease NF-kappaB and increase AP-1 transcriptional activity, thereby regulating gene expression. In T cells, low concentrations of antioxidants enhance IL-2 and inhibit IL-4 expression. Since NFAT binding sites play an essential role in regulating IL-2 and IL-4 gene transcription, we studied the effects of dithiocarbamates, using the pyrrolidine derivative of dithiocarbamate (PDTC), on the activity of the distinct AP-1-containing IL-2 NFAT and AP-1-less IL-4 NFAT enhancers elements. Consistent with the presence of AP-1 proteins within the IL-2 NFAT complex, PDTC strongly enhanced phorbol 12-myristate 13-acetate/phytohemagglutinin-induced NFAT binding to the IL-2 NFAT enhancer and transcriptional activity of a reporter plasmid driven by this NFAT enhancer. In contrast, the activity of the IL-4 NFp enhancer, which does not bind AP-1, was abolished by PDTC treatment. In the Jurkat T cell line treated with PDTC, co-expression of the Ca2+/calmodulin-dependent phosphatase, calcineurin, completely restored the IL-4 NFp enhancer activity. Our data indicate that calcineurin-mediated NFAT activity is a target for antioxidants and provides new insights into the molecular mechanisms controlling differential cytokine gene expression.

Antioxidants↗

PubMed1999

Vascular endothelial growth factor and basic fibroblast growth factor induce expression of CXCR4 on human endothelial cells: In vivo neovascularization induced by stromal-derived factor-1alpha.

The contribution of chemokines toward angiogenesis is currently a focus of intensive investigation. Certain members of the CXC chemokine family can induce bovine capillary endothelial cell migration in vitro and corneal angiogenesis in vivo, and apparently act via binding to their receptors CXCR1 and CXCR2. We used an RNAse protection assay that permitted the simultaneous detection of mRNA for various CXC chemokine receptors in resting human umbilical vein endothelial cells (HUVECs) and detected low levels of only CXCR4 mRNA. Stimulation of HUVECs with vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) up-regulated levels of only CXCR4 mRNA. CXCR4 specifically binds the chemokine stromal-derived factor-1alpha (SDF-1alpha). Competitive binding studies using 125I-labeled SDF-1alpha with Scatchard analysis indicated that VEGF or bFGF induced an average number of approximately 16,600 CXCR4 molecules per endothelial cell, with a Kd = 1.23 x 10(-9) mol/L. These receptors were functional as HUVECs and human aorta endothelial cells (HAECs) migrated toward SDF-1alpha. Although SDF-1alpha-induced chemotaxis was inhibited by the addition of a neutralizing monoclonal CXCR4 antibody, endothelial chemotaxis toward VEGF was not altered; therefore, the angiogenic effect of VEGF is independent of SDF-1alpha. Furthermore, subcutaneous SDF-1alpha injections into mice induced formation of local small blood vessels that was accompanied by leukocytic infiltrates. To test whether these effects were dependent on circulating leukocytes, we successfully obtained SDF-1alpha-induced neovascularization from cross sections of leukocyte-free rat aorta. Taken together, our data indicate that SDF-1alpha acts as a potent chemoattractant for endothelial cells of different origins bearing CXCR4 and is a participant in angiogenesis that is regulated at the receptor level by VEGF and bFGF.

Animals↗

PubMed1999

CNS interleukin-3 (IL-3) expression and neurological syndrome in antisense-IL-3 transgenic mice.

Interleukin-3 (IL-3) is an important mediator of physiological and pathophysiological processes affecting the central nervous system (CNS). It stimulates the proliferation and activation of microglia and can enhance differentiation of cholinergic and sensory neurons. To examine the role of IL-3 in the CNS, we utilized transgenic mice expressing a murine antisense IL-3 (AS-IL-3) RNA under the control of the T cell B19 promoter so that expression is limited to hematopoietic cells. The AS-IL-3 transgenic mice develop either a progressive neurologic dysfunction, which includes ataxia, bradykinesia, and paralysis, or a lymphoproliferative syndrome. Histopathology demonstrated accumulations of reactive astrocytes in the cerebellum, brain stem, and spinal cord, accompanied by activated microglia. Partial loss of cerebellar nuclei neurons as well as neurons in the cranial nerve nuclei and spinal cord motor neurons is seen. Despite depletion of IL-3 peripherally, expression of IL-3 mRNA and protein is turned on in the CNS of the transgenic mice. Astrocytes cultured from the AS-IL-3 mice contain IL-3 mRNA and may thus be responsible for the activation of the microglia. This model should provide important insights into the role of cytokines in neurological disorders.

Animals↗

PubMed1998

Ca2+-dependent production and release of IL-8 in human neutrophils.

IL-8, a potent neutrophil chemoattractant that is elevated about 200-fold in exudative neutrophils isolated from localized inflammatory sites in vivo, is thought to play a major role in recruitment of neutrophils to inflammatory sites. Incubation of peripheral blood neutrophils with thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+-sequestering-ATPase, causes a dose-dependent induction of IL-8 synthesis that continues for up to 8 h. Cycloheximide inhibits the thapsigargin-induced IL-8 production, suggesting the induction of protein synthesis de novo. In addition, Northern blot analysis of mRNA isolated from neutrophils indicates that thapsigargin treatment increases IL-8 mRNA in a time- and dose-dependent manner. Thapsigargin also induces a biphasic rise in the intracellular Ca2+ concentration, [Ca2+]i, which is composed of an initial (within 15 s) EGTA-insensitive elevation in [Ca2+]i, followed by a delayed (2-min) EGTA-sensitive component. Addition of EGTA before thapsigargin inhibited the induction of IL-8 production. Experiments in which EGTA was added at various times after thapsigargin treatment indicated that a sustained Ca2+ influx was required for maximum IL-8 production. Ascomycin and cyclosporin A, inhibitors of the Ca2+-dependent phosphatase, calcineurin, also inhibited thapsigargin-induced IL-8 production. Thus, in neutrophils, a prolonged increase in [Ca2+]i stimulates IL-8 transcription and synthesis, possibly through a calcineurin-dependent pathway.

Calcium↗

PubMed1998

Differential regulation of the Janus kinase-STAT pathway and biologic function of IL-13 in primary human NK and T cells: a comparative study with IL-4.

IL-13, a cytokine similar to IL-4, is a regulator of human B cell and monocyte functions. Biologic effects of IL-13 on primary human NK and T cells have not been well defined. We demonstrate that, in primary NK cells, IL-13, but not IL-4, may induce low levels of IFN-gamma secretion. When NK cells were costimulated with IL-13 and IL-2, IL-13 generally resulted in two types of reactivity: IL-13 synergized with IL-2 to stimulate IFN-gamma production or it modestly inhibited IL-2-mediated IFN-gamma production. In both types of donors, the effect of IL-13 on IL-2-induced IFN-gamma production was in marked contrast to the strong inhibition seen with IL-4 in NK cells. Additionally, IL-13 suppresses IL-2-induced NK cytolytic and proliferative activities although less efficiently than IL-4. In T cells, IL-13 inhibits anti-CD3 mAb/IL-2- or PHA-mediated IFN-gamma production and enhances cytolytic potential. Furthermore, we demonstrate that IL-13, like IL-4, induces distinct STAT6-DNA binding complexes and tyrosine phosphorylation of STAT6 and Janus kinase 3 (JAK3) in NK and T cells. We observed that Abs directed against unique domains of STAT6 have differential effects on complexes in T cells but not in NK cells, suggesting different STAT6 isoforms. These findings show that IL-13 and IL-4 have the ability to regulate NK and T cell activation and that IL-13 is a potent regulator of STAT6 and JAK3 in these cell types.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed1998

Characterization of cytokine differential induction of STAT complexes in primary human T and NK cells.

Cytokines, IL-2, IL-4, IL-6, IL-7, IL-12, and IL-15 are key regulators of human peripheral blood T and NK cell activation and differentiation but the precise mechanisms that give rise to their differential activities within these cells are not clear. Recent studies reveal that a family of transcription factors, signal transducers and activators of transcription (STATs) directly mediate many cytokine signals. We analyzed the activation of STATs in primary human T and NK cells by a variety of specific cytokines. We demonstrate that IL-12 induces STAT4 only in freshly isolated primary NK cells, but not in primary T cells, consistent with the lack of the IL-12 receptor in resting T cells. In contrast, IL-4 induces different C epsilon GAS DNA-protein binding complexes in both T and NK cells. Moreover, IL-4 costimulation with IL-2 or IL-12 does not alter their own preferential GAS-like DNA binding patterns when C epsilon-, Fc gamma RI-, and SIE GAS motif containing oligonucleotide probes are compared, suggesting that induction of GAS-like DNA-protein binding complexes by IL-2, IL-4, and IL-12 is highly selective and represents one important factor in determining specific gene activation. In addition, IL-6 and IL-2 synergistically induce homo- and heterodimerized STAT1 alpha and STAT3 in both NK and T cells, consistent with their reported synergism in modulating perforin gene expression. We further demonstrated that IL-2, -7, and -15 induce multiple STAT proteins, including STAT5a, STAT5b, STAT1 alpha, STAT3, and another unidentified Fc gamma RI GAS DNA-binding protein. Finally, we observed that activated STAT5a and STAT5b proteins form distinct Fc gamma RI GAS binding patterns in T and NK cells, suggesting that they might have different roles in gene regulation. Our data provide evidence that the differential responses in gene expression and cell activation seen in primary NK and T cells on direct stimulation with different cytokines may be a direct result of distinct activation of STAT transcription factors.

Cytokines↗

PubMed1998

Phenotypic and functional characterization of a panel of cytotoxic murine NK cell clones that are heterogeneous in their enhancement of Ig secretion in vitro.

NK cells not only function as cytotoxic effector cells, but also have immunoregulatory roles including the enhancement of Ig secretion. To have a stable and uniform population of NK cells to study their role in Ig secretion, we generated murine NK clones. Thus, culture of splenocytes from mice that were homozygous for a mutation in the p53 tumor suppressor gene (p53-KO) with IL-2 and poly(IC) resulted in a long-term NK line, from which four stable clones were derived. This approach also yielded a long-term NK line from splenocytes of normal C57BL/6 mice. Identification of the clones as members of the NK lineage was based on large granular morphology, expression of NK-TR and absence of TCR gene rearrangement. Flow cytometry revealed that all clones expressed IL-2R alpha and beta, chains and B220, but no CD3, NK1.1, DX5 or Ly-49. RT-PCR analysis showed heterogeneity in NK1.1 gene expression, and demonstrated expression of perforin and several granzymes in all clones. Three out of four clones lysed YAC-1, but not P815 target cells, corresponding to a pattern of NK specificity. All NK clones enhanced Ig secretion in an in vitro model for T cell-independent type 2 antigens, albeit to varying degrees. We found no correlation between the degree of helper activity of the NK clones and the level of their cytotoxic activity on YAC-1 targets. Thus, we established murine NK clones, and show that they mediate both cytotoxicity and enhancement of Ig secretion.

Animals↗

PubMed1998

Infection with human immunodeficiency virus type 1 upregulates DNA methyltransferase, resulting in de novo methylation of the gamma interferon (IFN-gamma) promoter and subsequent downregulation of IFN-gamma production.

The immune response to pathogens is regulated by a delicate balance of cytokines. The dysregulation of cytokine gene expression, including interleukin-12, tumor necrosis factor alpha, and gamma interferon (IFN-gamma), following human retrovirus infection is well documented. One process by which such gene expression may be modulated is altered DNA methylation. In subsets of T-helper cells, the expression of IFN-gamma, a cytokine important to the immune response to viral infection, is regulated in part by DNA methylation such that mRNA expression inversely correlates with the methylation status of the promoter. Of the many possible genes whose methylation status could be affected by viral infection, we examined the IFN-gamma gene as a candidate. We show here that acute infection of cells with human immunodeficiency virus type 1 (HIV-1) results in (i) increased DNA methyltransferase expression and activity, (ii) an overall increase in methylation of DNA in infected cells, and (iii) the de novo methylation of a CpG dinucleotide in the IFN-gamma gene promoter, resulting in the subsequent downregulation of expression of this cytokine. The introduction of an antisense methyltransferase construct into lymphoid cells resulted in markedly decreased methyltransferase expression, hypomethylation throughout the IFN-gamma gene, and increased IFN-gamma production, demonstrating a direct link between methyltransferase and IFN-gamma gene expression. The ability of increased DNA methyltransferase activity to downregulate the expression of genes like the IFN-gamma gene may be one of the mechanisms for dysfunction of T cells in HIV-1-infected individuals.

CD4-Positive T-Lymphocytes↗

PubMed1997

Interaction of NF-kappaB and NFAT with the interferon-gamma promoter.

Interferon-gamma (IFN-gamma) is a pleiotropic lymphokine whose production is restricted to activated T cells and NK cells. Along with other cytokines, IFN-gamma gene expression is inhibited by the immunosuppressant cyclosporin A. We have previously identified an intronic enhancer region (C3) of the IFN-gamma gene that binds the NF-kappaB protein c-Rel and that shows partial DNA sequence homology with the cyclosporin A-sensitive NFAT binding site and the 3'-half of the NF-kappaB consensus site. Sequence analysis of the IFN-gamma promoter revealed the presence of two additional C3-related elements (C3-1P and C3-3P). In addition, an NF-kappaB site (IFN-gamma kappaB) was identified within the promoter region. Based on this observation, we have analyzed the potential role of NF-kappaB and NFAT family members in regulating IFN-gamma transcription. Electrophoretic mobility shift assay analysis demonstrated that after T cell activation, the p50 and p65 NF-kappaB subunits bind specifically to the newly identified IFN-gamma kappaB and C3-related sites. In addition, we identified the NFAT proteins as a component of the inducible complexes that bind to the C3-3P site. Site-directed mutagenesis and transfection studies demonstrate that calcineurin-inducible transcriptional factors enhance the transcriptional activity of the IFN-gamma promoter through the cyclosporin-sensitive C3-3P site, whereas NF-kappaB proteins functionally interact with the C3-related sites. In addition, when located downstream to the beta-galactosidase gene driven by the IFN-gamma promoter, the intronic C3 site worked in concert with both the IFN-gamma kappaB and the C3-3P site to enhance gene transcription. These results demonstrate that the coordinate activities of NFAT and NF-kappaB proteins are involved in the molecular mechanisms controlling IFN-gamma gene transcription.

Base Sequence↗

PubMed1997

Characterization of the mouse Nktr gene and promoter.

We have cloned and determined the structure of the 5' region of the mouse Nktr gene located on the distal end of mouse chromosome 9. This gene encodes an NK-cell-specific 150-kDa protein (NK-TR) homologous to cyclophilin, Nopp140, and SR-containing proteins. NK-TR expression is important for maintaining the lytic activity of natural killer cells. The region of the Nktr gene cloned in this study spans 25 kb and contains the promoter, eight exons, and a single alternative exon. The boundaries of exons 6-8 and the alternate splicing events in this region are identical to those previously described for the human NKTR gene. The Nktr promoter region has features that are typical of a housekeeping gene, including high G + C content, high frequency of CpG dinucleotides, and a lack of canonical TATAA and CCAAT boxes. The activity of Nktr promoter/beta-gal reporter constructs was equivalent in lymphocyte and fibroblast cell lines, suggesting that NK-TR protein expression is regulated by posttranscriptional mechanisms. In support of this hypothesis, two levels of splicing control have been identified within the Nktr gene. A 10-kb intron was found to remain in mRNAs produced in bone marrow, and an alternative exon capable of interrupting the Nktr open reading frame was found in immature NK cells. A conserved intronic sequence has been identified that may be important for the regulation of the Nktr gene by pre-mRNA splicing.

3T3 Cells↗

PubMed1997

Bone marrow and thymus expression of interferon-gamma results in severe B-cell lineage reduction, T-cell lineage alterations, and hematopoietic progenitor deficiencies.

Interferon-gamma (IFN-gamma) is an immunoregulatory lymphokine that is primarily produced by T cells and natural killer cells. It has effects on T-cell, B-cell, and macrophage differentiation and maturation. We have developed transgenic mice that express elevated levels of IFN-gamma mRNA and protein by inserting multiple copies of murine IFN-gamma genomic DNA containing an Ig lambda-chain enhancer in the first intron. The founder line carrying eight copies of this transgene has eightfold to 15-fold more IFN-gamma-producing cells in the bone marrow and spleen than do nontransgenic littermates. Transgenic mice show a pronounced reduction in B-lineage cells in the bone marrow, spleen, and lymph nodes. In addition, single positive (CD4+,CD8- and CD4-,CD8+) thymocyte numbers are increased twofold, yet the number of splenic T cells is reduced by 50%. There is also a twofold to threefold decrease in the frequency and total number of myeloid progenitors in the bone marrow. Granulomatous lesions and residual degenerating cartilaginous masses are also present in the bones of these mice. Overall, our data show that the abnormal expression of IFN-gamma in these transgenic mice results in multiple alterations in the immune system. These animals provide an important model to examine the role of IFN-gamma expression on lymphoid and myeloid differentiation and function.

Animals↗

PubMed1997

Identification of a Stat-6-responsive element in the promoter of the human interleukin-4 gene.

Interleukin (IL)-4 is an immunomodulatory cytokine produced by a number of cell types including T cells, basophils, and mast cells. This pleiotropic cytokine has a number of immunoregulatory functions; however, the molecular mechanisms controlling the transcription of this gene are not yet completely understood. Several studies have implicated a possible autoregulatory mechanism for its own expression. Here, we have identified a Stat-6-responsive element (Stat-6RE) in the promoter of the human IL-4 gene. Utilizing electrophoretic mobility shift analysis, we have demonstrated the presence of two specific IL-4-responsive DNA-protein complexes in nuclear extracts of both human Th1 and Th2 clones. Phytohemagglutinin-blasted peripheral blood T cells also generated an inducible complex in response to stimulation with IL-4 and the IL-4-like cytokine IL-13. Transient transfection of the murine pre-B cell line BA/F3 stably transfected with the full-length human IL-4 receptor alpha chain demonstrated the ability of multicopy Stat-6RE to initiate transcription from a heterologous promoter upon IL-4 or IL-13 stimulation. These results indicate a possible autocrine mechanism for the regulation of IL-4 gene transcription through the Stat-6RE as well as a possible mechanism for IL-13 regulation of the human IL-4 promoter.

Animals↗

PubMed1997

Interferon expression by B cells.

Interferons have effects on many facets of immune system development, maturation, and function. B cells are a target for the interferons, causing alterations in cell differentiation and gene expression. However, production of interferons by B cells has not been widely studied. In this review I will discuss the limited literature on B-cell interferon production. In addition I will describe results obtained from a transgenic model in which interferon-gamma production has been targeted to the B-cell compartment. In this animal, B-cell development is blocked, reflecting the deleterious effects that aberrant expression of interferon can have on this cell population.

Animals↗

PubMed1997

Molecular regulation of cytokine gene expression: interferon-gamma as a model system.

The regulation of IFN-gamma transcription appears to be quite complex. In addition to the interaction of numerous regions of the genomic DNA with multiple DNA binding protein family members, DNA methylation may serve to act as an early determinant of the capacity of a cell to initiate transcription. Transcriptional activation occurs in response to both soluble extracellular signals and cell contact, and it appears quite likely that this activation may result from the interaction of different families of DNA binding proteins with different enhancer elements. Furthermore, because chronic IFN-gamma transcription and subsequent expression would likely be detrimental to the host (see 81), mechanisms have evolved to quench expression at both transcriptional and posttranscriptional levels. Given the complexity of cell-to cell interactions in the immune system, it is reasonable to expect that additional mechanisms regulating IFN-gamma transcription, involving previously identified or as yet unidentified DNA binding proteins, remain to be defined.

Animals↗

PubMed1997

Negative regulation of cytokine gene transcription.

Cytokines are a class of soluble proteins that mediate signals throughout the immune system as well as between immune effector cells and other cell populations. This class of proteins includes interleukins, interferons, and chemokines. The expression of cytokines is tightly controlled in the producing cells, and one of the most important regulatory steps in this control is gene transcription. The transcription of most cytokine genes is silent until a producing cell is activated by extracellular stimuli. It is very common that transcription of these genes initiates immediately upon activation and shuts down quickly even in the continuous presence of the stimulating agent. Work performed over the past decade has revealed much about the molecular mechanism responsible for transcriptional regulation of these genes. Positive and negative transcription factors function in a concerted manner to regulate transcription of a specific cytokine at the promoter or intron region. We focus on recent progress in the field of transcriptional regulation of cytokine genes with an emphasis on the negative regulation of cytokine gene transcription.

Animals↗