LIGHT regulates CD86 expression on dendritic cells through NF‐κB, but not JNK/AP‐1 signal transduction pathway

Zou, Gang; Hu, Wen‐Yang

doi:10.1002/jcp.20420

Cited by 40 publications

(40 citation statements)

References 31 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similar to CD40L, LIGHT induces DC maturation, upregulating co-stimulatory molecules, inducing IL-12 secretion and enhancing T cell stimulation (Morel et al, 2001). The current study by Zou and Hu extends these findings by highlighting a critical role for the NF-kB pathway in the upregulation of CD86 on DC following maturation induced by LIGHT (Zou and Hu, 2005). …”

supporting

confidence: 56%

“…In a similar manner, the co-expression of LIGHT and HVEM on the surface of activated T cells results in downregulation of the receptor (Morel et al, 2000). The consequence of either scenario may be to prevent triggering of maturation signals in DC by LIGHT (Zou and Hu, 2005), reducing type I IFN secretion, and delaying an antiviral response that may control the infection (Banks et al, 2005). Thus, the observations by Zou and Hu are likely to have an important impact on our understanding both of DC immunobiology and of the viral interaction with DC.…”

mentioning

confidence: 96%

See 1 more Smart Citation

LIGHTing up dendritic cell activation: Immune regulation and viral exploitation

Pollara¹,

Katz²,

Chain³

2005

J. Cell. Physiol.

View full text Add to dashboard Cite

The maturation state of dendritic cells (DC) is regulated by a variety of factors. These include ligands expressed by T cells, such as members of the TNF superfamily. Recent studies have highlighted the role of one such molecule, LIGHT, as a positive regulator of DC biology, promoting the maturation of these cells through the activation of NF-kB pathways. In addition, HSV-1 envelope glycoproteins can also bind the LIGHT receptor, herpes virus entry mediator (HVEM), and activate similar downstream signalling pathways in DC. The consequence of this host-viral interaction may be a novel pathway of viral immune evasion.

show abstract

supporting

confidence: 56%

mentioning

confidence: 96%

LIGHTing up dendritic cell activation: Immune regulation and viral exploitation

Pollara¹,

Katz²,

Chain³

2005

J. Cell. Physiol.

View full text Add to dashboard Cite

show abstract

“…This finding contrasts with numerous previous studies in a wide variety of cell types that have reported that LIGHT, acting via either HVEM or LT␤R, activates NF-B (Marsters et al, 1997;Hikichi et al, 2001;Matsui et al, 2002;Zou and Hu, 2005;Wei et al, 2006;Pierer et al, 2007). We have previously shown that NF-B is a key regulator of neurite growth in neonatal nodose neurons, and that inhibiting canonical NF-B signaling in these neurons significantly reduces BDNF-promoted neurite growth during a developmental window from E18 to P1 (Gutierrez et al, Figure 6.…”

contrasting

confidence: 55%

Developmental Regulation of Sensory Neurite Growth by the Tumor Necrosis Factor Superfamily Member LIGHT

Gavaldà

Gutiérrez²,

Davies³

2009

J. Neurosci.

View full text Add to dashboard Cite

In a PCR screen to identify novel cytokine candidates involved in neuronal development, we identified transcripts for the tumor necrosis factor superfamily member 14 (TNFSF14), generally known as LIGHT (lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells), together with its receptors, lymphotoxin-␤ receptor (LT␤R) and TNF family receptor herpesvirus entry mediator (HVEM), in the experimentally tractable sensory neurons of the mouse nodose ganglion. Immunocytochemistry revealed coexpression of LIGHT and its receptors in all nodose ganglion neurons in neonates. Enhancing LIGHT signaling in these neurons by overexpressing LIGHT inhibited BDNF-promoted neurite growth during a narrow window of development in the immediate perinatal period without affecting neuronal survival. Overexpressing a LIGHT mutant that selectively activates HVEM, but not one that selectively activates LT␤R, also inhibited BDNF-promoted growth, suggesting that neurite growth inhibition is mediated via HVEM. Blocking HVEM signaling by a function-blocking anti-HVEM antibody significantly enhanced neurite growth from nodose neurons grown both with and without BDNF. Likewise, neurons from LIGHT-deficient neonates exhibited significantly greater neurite growth than neurons from wild-type littermates in both the presence and absence of BDNF. LIGHT overexpression significantly inhibited NF-B activity, while preventing LIGHT-induced NF-B inhibition by overexpressing the p65 and p50 NF-B subunits prevented LIGHTmediated growth inhibition. Together, these findings show that LIGHT/HVEM signaling negatively regulates neurite growth from developing sensory neurons via NF-B inhibition.

show abstract

“…Transcription factors involved in stimulus-induced expression of CD80 or CD86 have been observed in some promoter structure analyses; for example, interferon regulatory factor 7 (IRF7) regulates lipopolysaccharide (LPS)-induced human CD80 transcription through the activation of Jun N-terminal kinase in monocytes, 13 nuclear factor -light-chain-enhancer of activated B cells (NF-B) plays a role in stimulation-induced transactivation of murine CD80 in B-cell lines, 14 human CD86 in B cells, 15 and CD86 in DCs. 16 However, the specific transcription factors regulating the basic and constitutive expression of CD80 and CD86 have not been identified to date.PU.1 is a transcription factor belonging to the Ets family, which is involved in hematopoietic cell development. Although PU.1 is required for the development of thymic and myeloid DCs, including some specific gene expression by DCs in the analysis of PU.1 Ϫ/Ϫ animals, 17,18 the effects of PU.1 on the expression of CD80 and CD86 have not been verified in those reports.…”

mentioning

confidence: 99%

Critical role of transcription factor PU.1 in the expression of CD80 and CD86 on dendritic cells

Kanada

Nishiyama

Nakano

et al. 2011

Blood

View full text Add to dashboard Cite

In this study, we investigated the role of a transcription factor, PU.1, in the regulation of CD80 and CD86 expression in dendritic cells (DCs). A chromatin immunoprecipitation assay revealed that PU.1 is constitutively bound to the CD80 and CD86 promoters in bone marrow-derived DCs. In addition, co-expression of PU.1 resulted in the transactivation of the CD80 and CD86 promoters in a reporter assay. The binding of PU.1 to cis-enhancing regions was confirmed by electromobility gel-shift assay. As expected, inhibition of PU.1 expression by short interfering RNA (siRNA) in bone marrow-derived DCs resulted in marked down-regulation of CD80 and CD86 expression. Moreover, overexpression of PU.1 in murine bone marrow-derived lineage-negative cells induced the expression of CD80 and CD86 in the absence of monocyte/ DC-related growth factors and/or cytokines. Based on these results, we conclude that PU.1 is a critical factor for the expression of CD80 and CD86. We also found that subcutaneous injection of PU.1 siRNA or topical application of a cream-emulsified PU.1 siRNA efficiently inhibited murine contact hypersensitivity. Our results suggest that PU.1 is a potential target for the treatment of immune-related diseases. (Blood. 2011; 117(7):2211-2222) IntroductionT-cell initiation requires 2 signals from antigen-presenting cells (APCs). The first signal comes from ligation of the T-cell receptor and the major histocompatibility complex (MHC)/antigen presented on the surface of APCs, and the second signal is via additional costimulatory molecules, including the interaction between the CD28 family on T cells and B7, eg, CD80 (B7-1) and CD86 (B7-2), expressed on the APC. 1-3 CD80 and CD86 are members of the immunoglobulin supergene family encoded by separate genes, and are expressed on dendritic cells (DCs) or up-regulated on activated macrophages/monocytes, B cells, and activated T cells. 1-6 CD80 or CD86 can provide costimulatory signals by engaging CD28 or CTLA4 (cytotoxic T-lymphocyte antigen 4; CD152) on T cells. The engagement of CD28 with CD80 or CD86 leads to multiple effects on the immune response, including T-cell activation and differentiation and tissue migration. [7][8][9] In contrast to CD28, the outcome of CTLA4 engagement on T cells is to suppress proliferation by transmitting an inhibitory signal. 10 In addition, a subset of T cells with potent immunoregulatory properties, CD4 ϩ CD25 ϩ regulatory T cells, constitutively expresses CTLA4. 11,12 Thus, interactions between CTLA4 and CD80 or CD86 provides an immunosuppressive function in modulating T-cell proliferation and plays a role in immune tolerance. Based on these observations, the regulated expression of costimulatory molecules is critical for immune function. Therefore, revealing the molecular mechanisms of gene expression of costimulatory molecules is essential for an understanding of the regulation of T cell-mediated immune responses.Despite the importance of CD80 and CD86, the critical transcription factor for gene expression of CD80 or CD86 is sti...

show abstract

LIGHT regulates CD86 expression on dendritic cells through NF‐κB, but not JNK/AP‐1 signal transduction pathway

Cited by 40 publications

References 31 publications

LIGHTing up dendritic cell activation: Immune regulation and viral exploitation

LIGHTing up dendritic cell activation: Immune regulation and viral exploitation

Developmental Regulation of Sensory Neurite Growth by the Tumor Necrosis Factor Superfamily Member LIGHT

Critical role of transcription factor PU.1 in the expression of CD80 and CD86 on dendritic cells

Contact Info

Product

Resources

About