The N-Terminal Domain of NLRC5 Confers Transcriptional Activity for MHC Class I and II Gene Expression

Neerincx, Andreas; Jakobshagen, Kristin; Utermöhlen, Olaf; Büning, Hildegard; Steimle, Viktor; Kufer, Thomas A.

doi:10.4049/jimmunol.1401065

Cited by 33 publications

(27 citation statements)

References 51 publications

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“…; Neerincx et al . ). It has been reported that interferon‐ γ (IFN‐ γ ) and lipopolysaccharide (LPS) induce the expression of NLRC5 (Benko et al .…”

Section: Introductionmentioning

confidence: 97%

Characterization of the NLRC5 promoter in chicken: SNPs, regulatory elements and CpG islands

et al. 2016

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SummaryNLRC5 plays an important role in the innate immunity and cellular immunity in many species, but the regulatory mechanism of NLRC5 expression in chickens remains unclear. In this study, a series of deletion fragments of the NLRC5 promoter region were constructed and dual-luciferase assay was performed. Then, we detected the SNP in the core region and its function. Important transcriptional regulatory elements were predicted and identified. Methylation of CpG islands was measured. The results revealed that the two core regions of À4372 to À3756 and À2925 to À2265 in the NLRC5 promoter were essential for NLRC5 mRNA expression in which a SNP (A/G), located at À2470, was found to have an effect on the transcriptional activity. Also, the STAT1 element in the second core region of the NLRC5 promoter was identified to bind with the STAT1 transcription factor, which was necessary for the transcriptional activity. In addition, many other elements in the NLRC5 promoter, including YY1 and CEBP, may contribute significantly to the expression activity of NLRC5. Moreover, two CpG islands were searched. Part of one was located in the first core region, which suggests that epigenetic modification may regulate the activity of the first promoter region, and the other was mostly in an unmethylated state. Collectively, these results suggest the complex regulation of NLRC5 expression includes SNPs, transcription factors and methylation.

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“…; Neerincx et al . ). It has been reported that interferon‐ γ (IFN‐ γ ) and lipopolysaccharide (LPS) induce the expression of NLRC5 (Benko et al .…”

Section: Introductionmentioning

confidence: 97%

Characterization of the NLRC5 promoter in chicken: SNPs, regulatory elements and CpG islands

et al. 2016

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“…The last is comprised of W/S, X1, X2, and Y boxes (27,29) and is regulated by the binding of a multiprotein complex (30)(31)(32)(33)(34) to regulate the expression of MHC molecules (35)(36)(37). A recently identified NOD-, LRR-, and CARD-containing 5 (NLRC5) protein has been demonstrated to function as a specific cotransactivator of MHC-I genes (28,(38)(39)(40)(41).…”

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confidence: 99%

“…Viral infection, interferon stimulation, and similar challenges induce NLRC5 expression in a STAT1-dependent manner (28,42). However, NLRC5 itself does not have a DNAbinding domain and therefore must cooperate with the multiprotein complex to regulate MHC-I gene expression (28,39,43,44).…”

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confidence: 99%

Respiratory Syncytial Virus Infection Upregulates NLRC5 and Major Histocompatibility Complex Class I Expression through RIG-I Induction in Airway Epithelial Cells

Guo

Liu

Shi

et al. 2015

J Virol

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Respiratory syncytial virus (RSV) is the leading cause of acute respiratory tract viral infection in infants, causing bronchiolitis and pneumonia. The host antiviral response to RSV acts via retinoic acid-inducible gene I (RIG-I). We show here that RSV infection upregulates major histocompatibility complex class I (MHC-I Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in infants and young children, causing bronchiolitis and pneumonia in infants and young children worldwide. Due to the highly infectious nature of the virus, roughly two-thirds of children are infected by their first birthday, and this reaches essentially 100% by the age of 2 (1, 2). RSV infection is a leading cause of infant hospitalization due to bronchiolitis (2, 3). In the United States alone, an estimated 2.1 million children under 5 years of age with RSV infection require medical attention each year (4). Importantly, lower respiratory tract infection by RSV early in life is a risk factor for persistent wheezing and asthma in later life (5, 6). There are no RSV vaccines available to prevent childhood infection. These factors create an urgent need to understand the mechanisms of RSV disease, the molecular mechanisms associated with immunoregulation, and the downstream association between RSV infection and allergic asthma.RSV belongs to the subfamily Pneumovirinae of the paramyxoviruses. A negative-sense, single-stranded RNA virus with a genome of approximately 15,000 nucleotides (7), the virus can infect a broad range of cells. In patients, however, infection is normally highly restricted to the superficial cells of the respiratory epithelium, the ciliated cells of the small bronchioles, and pneumocytes in the alveoli (8-10). Infection is initiated by cell surface binding via proteoglycans (11), followed by nucleolin-mediated fusion for RSV cell entry (9, 12) and infection. In response, the host initiates an early innate immune response at the site of infection. Receptors of innate immune recognition, like Toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I), which are involved in detection of viral RNA, promote the activation of antiviral immunity and cytokine production, as well as the recruitment of proinflammatory cells (10,(13)(14)(15)(16). This increased expression of inflamma-

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“…[35][36][37][38] In a related vein, gene clusters that are important factors in cytokine response and IFN production (e.g., NLRC5, IFI44, and ZBP1) are found upregulated in both retina and cultured photoreceptor cells. [39][40][41][42] On the other hand, the expression of class II major histocompatibility complex-associated gene CD74 was also increased, which might attenuate a TLR3-triggered innate inflammatory response. 43 For the first time, these immune-related genes are reported to be expressed in photoreceptor cells.…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 3 Activation Initiates Photoreceptor Cell Death In Vivo and In Vitro

Gao

Deng

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Accumulating evidence has demonstrated that excessive immunoreaction plays a prominent role in the pathogenesis of dry AMD. Toll-like receptor 3 (TLR3) can be activated by double-stranded (ds)RNA in retinal pigment epithelia and trigger an innate immunitymediated inflammatory response. However, its role in photoreceptor cells, the effectors of AMD geographic atrophy, remains unclear.METHODS. The expression of TLR3 was examined in mouse retina and in a murine photoreceptor cell line (661W). Retinal structure, function, and cell death in the polyinosinepolycytidylic acid (poly I:C)-treated retina were investigated by optical coherence tomography, electroretinography (ERG), and immunostaining. Cytokine and chemokine expression as well as cell death were measured in poly I:C-exposed 661W cells and explant retinas. By comparing the RNA sequencing (seq) data of 661W cells and murine retina, we comprehensively investigated the contribution of photoreceptor in poly I:C-induced retinal immune response.RESULTS. Toll-like receptor 3 was highly expressed in the inner segment of the photoreceptor and in 661W cells. We found poly I:C induced significant retinal structural damages and impairment of ERG responses. Focal ERG demonstrated that injected and parainjected zones were functionally damaged by poly I:C. In addition, poly I:C acted on cultured photoreceptor cells directly and evoked an inflammatory response that exhibited similarities with the immune response in mouse retina. Moreover, TLR3 activation initiated cell death in murine photoreceptor cells in vivo and in vitro. Additionally, poly I:C initiated immune response in explant retinas. CONCLUSIONS.We deciphered the TLR3-mediated inflammatory response in photoreceptor cells. Our findings suggested TLR3-mediated inflammatory response in photoreceptor cells may play an important role in dry AMD, offering new insights of potential treatments targeting photoreceptor immunity.

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The N-Terminal Domain of NLRC5 Confers Transcriptional Activity for MHC Class I and II Gene Expression

Cited by 33 publications

References 51 publications

Characterization of the NLRC5 promoter in chicken: SNPs, regulatory elements and CpG islands

Characterization of the NLRC5 promoter in chicken: SNPs, regulatory elements and CpG islands

Respiratory Syncytial Virus Infection Upregulates NLRC5 and Major Histocompatibility Complex Class I Expression through RIG-I Induction in Airway Epithelial Cells

Toll-Like Receptor 3 Activation Initiates Photoreceptor Cell Death In Vivo and In Vitro

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