Inducible IL-2 production by dendritic cells revealed by global gene expression analysis

Granucci, Francesca; Vizzardelli, Caterina; Pavelka, Norman; Feau, Sonia; Persico, Maria; Virzi, Ettore; Rescigno, María; Moro, Giorgio; Ricciardi‐Castagnoli, Paola

doi:10.1038/ni0901-882

Cited by 449 publications

(293 citation statements)

References 32 publications

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“…It has been shown that Bcl-2 is rapidly down-regulated upon the induction of DC maturation (24). In addition, CD40 ligand, RANK ligand, TNF-␣, IL-12, IL-15, LPS, and CpG were shown to inhibit apoptosis in DCs via up-regulations of Bcl-2, Bcl-x L , and cellular inhibitor of apoptosis proteins (25)(26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

Survival adjustment of mature dendritic cells by IL-15

Dubois

Waldmann

Müller

2005

Proc. Natl. Acad. Sci. U.S.A.

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The survival of CD8 ؉ ͞CD44 hi memory phenotype T cells depends on an IL-15 activity on nonlymphoid cells. Here, we report that IL-15 and its receptor were induced on dendritic cells (DCs) by a combination of IFN-␥ and NF-B relA inducers. IL-15 conferred in an autocrine loop resistance to apoptosis that accompanied the maturation process in DCs in vitro. As an apparent result in vivo, mice deficient in IL-15 or its receptor harbor few DCs. Injecting DCs into IL-15 ؊͞؊ mice was associated with the appearance of CD8 ؉ ͞CD44 hi T cells that depended on IL-15 expression but also correlated with the longevity of the DCs. These findings support the hypothesis that DCs mediate the effect of IL-15 on CD8 ؉ ͞CD44 hi memory phenotype T cells.apoptosis ͉ cytokine ͉ antigen-presenting cells ͉ memory phenotype CD8 T cells

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Section: Discussionmentioning

confidence: 99%

Survival adjustment of mature dendritic cells by IL-15

Dubois

Waldmann

Müller

2005

Proc. Natl. Acad. Sci. U.S.A.

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“…Analysis was done by hybridizing the fragmented cRNAs to the Affymetrix GeneChip® Yeast Genome S98 array, which permits the monitoring of the mRNA abundance from 6400 ORFs. Probe array hybridizations were carried out under rotation at 45°C for 16 h as described (35). The arrays, stained by incubation with 2 g/ml phycoerythrin-streptavidin (Molecular Probes, Eugene, OR) and 1 mg/ml acetylated bovine serum albumin (Sigma), were read at a resolution of 7.5 m by a confocal scanner and analyzed with the MicroArray Suite 4.0 Gene Expression analysis program (both from Affymetrix).…”

Section: Methodsmentioning

confidence: 99%

Transcriptional Profiling of ubp10 Null Mutant Reveals Altered Subtelomeric Gene Expression and Insurgence of Oxidative Stress Response

Orlandi

Bettiga

Alberghina

et al. 2004

Journal of Biological Chemistry

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UBP10 codes for a deubiquitinating enzyme of Saccharomyces cerevisiae whose loss of function determines slow growth rate and partial impairment of silencing at telomeres and HM loci. A genome-wide analysis performed on a ubp10 disruptant revealed alterations in expression of subtelomeric genes together with a broad change in the whole transcriptional profile, closely parallel to that induced by oxidative stress. This response was accompanied by intracellular accumulation of reactive oxygen species as well as by DNA fragmentation and phosphatidylserine externalization, two markers of apoptosis. SIR4 inactivation mitigated the wide transcriptome remodeling of the ubp10 null mutant affecting particularly the stress transcriptional profile. Moreover, the ubp10sir4 disruptant did not display apoptotic markers. These results argue in favor of an involvement of deubiquitination in transcriptional control and suggest a linkage between oxidative stress and apoptotic pathway in budding yeast.

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“…Cell activation triggered by the interaction of PAMPs and TLRs is characterized by induction of host defense genes, production of both proinflammatory and anti-inflammatory regulatory cytokines, and the up-regulation of cell surface markers (3)(4)(5)(6)(7)(8)(9). Several bacterial PAMPs have been identified, including bacterial DNA.…”

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confidence: 99%

Activation of RAW264.7 Macrophages by Bacterial DNA and Lipopolysaccharide Increases Cell Surface DNA Binding and Internalization

McCoy

Kurtz

Hausman³

et al. 2004

Journal of Biological Chemistry

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Bacterial DNA containing unmethylated CpG motifs is a pathogen-associated molecular pattern (PAMP) that interacts with host immune cells via a toll-like receptor (TLR) to induce immune responses. DNA binding and internalization into cells is independent of TLR expression, receptor-mediated, and required for cell activation. The objective of this study was to determine whether exposure of immune cells to bacterial DNA affects DNA binding and internalization. Treatment of RAW264.7 cells with CpG oligodeoxynucleotide (ODN) for both 18 and 42 h resulted in a significant increase in DNA binding, whereas non-CpG ODN had no effect on DNA binding. Enhanced DNA binding was non-sequence-specific, inhibited by unlabeled DNA, showed saturation, was consistent with increased cell surface DNA receptors, and resulted in enhanced internalization of DNA. Treatment with Escherichia coli DNA or lipopolysaccharide (LPS) also resulted in a significant increase in DNA binding, but treatment with interleukin-1␣, tumor necrosis factor-␣, or phorbol 12-myristate 13-acetate had no effect on DNA binding. Soluble factors produced in response to treatment with CpG ODN or LPS did not affect DNA binding. These studies demonstrate that one consequence of activating the host innate immune response by bacterial infection is enhanced binding and internalization of DNA. During this period of increased DNA internalization, RAW264.7 cells were hypo-responsive to continued stimulation by CpG ODN, as assessed by tumor necrosis factor-␣ activity. We speculate the biological significance of increasing DNA binding and internalization following interaction with bacterial PAMPs may provide a mechanism to limit an ongoing immune inflammatory response by enhancing clearance of bacterial DNA from the extracellular environment.The interaction of conserved pathogen-associated molecular patterns (PAMPs), 1 components of bacteria and viruses, withToll-like receptors (TLRs), present on host innate immune cells, triggers a potent immune response (1, 2). Cell activation triggered by the interaction of PAMPs and TLRs is characterized by induction of host defense genes, production of both proinflammatory and anti-inflammatory regulatory cytokines, and the up-regulation of cell surface markers (3-9). Several bacterial PAMPs have been identified, including bacterial DNA. Bacterial DNA stimulates the proliferation of B cells and is a potent activator of macrophages and dendritic cells, eliciting an inflammatory immune response (10 -13).Host innate immune cells are activated by bacterial DNA but not mammalian DNA, because of recognition of unmethylated CpG motifs by TLR9 (4,14). TLR9 is located intracellularly, and DNA binding and internalization are required for cell activation (15). Binding and internalization of DNA are independent of TLR9 expression, and cells that lack TLR9 bind and internalize DNA but are not activated by CpG DNA (15-18). There are numerous reports of the association of different forms of nucleic acids, such as DNA, RNA, and oligonucleotides, with c...

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Inducible IL-2 production by dendritic cells revealed by global gene expression analysis

Cited by 449 publications

References 32 publications

Survival adjustment of mature dendritic cells by IL-15

Survival adjustment of mature dendritic cells by IL-15

Transcriptional Profiling of ubp10 Null Mutant Reveals Altered Subtelomeric Gene Expression and Insurgence of Oxidative Stress Response

Activation of RAW264.7 Macrophages by Bacterial DNA and Lipopolysaccharide Increases Cell Surface DNA Binding and Internalization

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