Apolipoproteins L control cell death triggered by TLR3/TRIF signaling in dendritic cells

Uzureau, Sophie; Coquerelle, Caroline; Vermeiren, Corentin; Uzureau, Pierrick; Acker, Annette Van; Pilotte, Luc; Monteyne, Daniel; Acolty, Valérie; Vanhollebeke, Benoît; Eynde, Benoı̂t J. Van den; Pérez‐Morga, David; Moser, Muriel; Pays, Étienne

doi:10.1002/eji.201546252

Cited by 39 publications

(59 citation statements)

References 54 publications

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“…Apolipoproteins are related to lipid transporter activity, and share characteristics with members of the apoptotic Bcl-2 family ( Uzureau et al, 2016 ). Some members of this family like the apolipoprotein A5 ( APOA5 ) and apolipoprotein C3 ( APOC3 ) are regulators of triglyceride, lipoprotein metabolism, cholesterol, LDL, and HDL ( O’Brien et al, 2005 ).…”

Section: Discussionmentioning

confidence: 99%

Gene Co-expression Analysis Indicates Potential Pathways and Regulators of Beef Tenderness in Nellore Cattle

et al. 2018

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Beef tenderness, a complex trait affected by many factors, is economically important to beef quality, industry, and consumer’s palatability. In this study, RNA-Seq was used in network analysis to better understand the biological processes that lead to differences in beef tenderness. Skeletal muscle transcriptional profiles from 24 Nellore steers, selected by extreme estimated breeding values (EBVs) for shear force after 14 days of aging, were analyzed and 22 differentially expressed transcripts were identified. Among these were genes encoding ribosomal proteins, glutathione transporter ATP-binding cassette, sub-family C (CFTR/MRP), member 4 (ABCC4), and synaptotagmin IV (SYT4). Complementary co-expression analyses using Partial Correlation with Information Theory (PCIT), Phenotypic Impact Factor (PIF) and the Regulatory Impact Factor (RIF) methods identified candidate regulators and related pathways. The PCIT analysis identified ubiquitin specific peptidase 2 (USP2), growth factor receptor-bound protein 10 (GBR10), anoctamin 1 (ANO1), and transmembrane BAX inhibitor motif containing 4 (TMBIM4) as the most differentially hubbed (DH) transcripts. The transcripts that had a significant correlation with USP2, GBR10, ANO1, and TMBIM4 enriched for proteasome KEGG pathway. RIF analysis identified microRNAs as candidate regulators of variation in tenderness, including bta-mir-133a-2 and bta-mir-22. Both microRNAs have target genes present in the calcium signaling pathway and apoptosis. PIF analysis identified myoglobin (MB), enolase 3 (ENO3), and carbonic anhydrase 3 (CA3) as potentially having fundamental roles in tenderness. Pathways identified in our study impacted in beef tenderness included: calcium signaling, apoptosis, and proteolysis. These findings underscore some of the complex molecular mechanisms that control beef tenderness in Nellore cattle.

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Section: Discussionmentioning

confidence: 99%

Gene Co-expression Analysis Indicates Potential Pathways and Regulators of Beef Tenderness in Nellore Cattle

et al. 2018

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“…Information about the function of Apol11b and Lyst, two genes with the expression verified by RT-qPCR, is rather limited. The Apol11b gene, upregulated in both tested groups (3NF/pCI and K3/pCI), encodes the Apolipoprotein L variant specific for the spleen ( 35 ). Apolipoproteins L share functional similarities with proteins of the Bcl-2 family, taking part in the regulation of apoptosis, and are encoded by genes induced under inflammatory conditions, i.e., type-1 INF.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity of DNA Vaccine against H5N1 Containing Extended Kappa B Site: In Vivo Study in Mice and Chickens

et al. 2017

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Influenza is one of the most important illnesses in the modern world, causing great public health losses each year due to the lack of medication and broadly protective, long-lasting vaccines. The development of highly immunogenic and safe vaccines is currently one of the major problems encountered in efficient influenza prevention. DNA vaccines represent a novel and powerful alternative to the conventional vaccine approaches. To improve the efficacy of the DNA vaccine against influenza H5N1, we inserted three repeated kappa B (κB) motifs, separated by a 5-bp nucleotide spacer, upstream of the cytomegalovirus promoter and downstream of the SV40 late polyadenylation signal. The κB motif is a specific DNA element (10pb-long) recognized by one of the most important transcription factors NFκB. NFκB is present in almost all animal cell types and upon cell stimulation under a variety of pathogenic conditions. NFκB is released from IκB and translocates to the nucleus and binds to κB sites, thereby leading to enhanced transcription and expression of downstream genes. We tested the variants of DNA vaccine with κB sites flanking the antigen expression cassette and without such sites in two animal models: chickens (broilers and layers) and mice (BALB/c). In chickens, the variant with κB sites stimulated stronger humoral response against the target antigen. In mice, the differences in humoral response were less apparent. Instead, it was possible to spot several gene expression differences in the spleens isolated from mice immunized with both variants. The results of our study indicate that modification of the sequence outside of the sequence encoding the antigen might enhance the immune response to the target but understanding the mechanisms responsible for this process requires further analysis.

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“…These data suggest that the APOL family members, in addition to having evolved to play an anti-parasite role, also have anti-viral roles and provide an important new perspective on this gene family. Interestingly, like APOL1 , TNFRS10D expression is induced by interferon, as are APOL3 (or by the interferon-mimic poly-inosine-cytosine) (Uzureau et al 2016) and APOL6 (Zhaorigetu et al 2011). …”

Section: Apol1 As An Hiv Restriction Factormentioning

confidence: 99%

APOL1 Renal Risk Variants: Fertile Soil for HIV-Associated Nephropathy

Kopp

Heymann

Winkler

2017

Seminars in Nephrology

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Apolipoprotein L1 (APOL1) genetic variants are potent risk factors for glomerular disease, but one or more additional factors are required for expression of glomerular disease. Uncontrolled or poorly controlled HIV infection is the most potent susceptibility factor for APOL1 nephropathy that has been identified to date. APOL1 variants are associated with HIV-associated nephropathy (HIVAN), a podocyte disease, but not with HIV-immune complex disease, primarily a disease of the mesangium. The mechanism by which HIV brings out the latent glomerular disease risk remains to be defined. There are at least two classes of candidate mechanisms to explain the potent interaction between HIV-1 and APOL1. First, APOL1 variant proteins and HIV accessory proteins implicated in HIVAN may target the same or related intracellular pathways in podocytes. Recent data suggests roles for interleukin 1b and transcription factor EB (TFEB). Second, features of uncontrolled HIV-infection, including elevated circulating factors such as interferon, may drive APOL1 gene transcription or act upon podocytes in other ways. Deeper probing of APOL1-HIV interactions may yield insights that will aid understanding HIVAN, APOL1 nephropathy, and podocyte biology.

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Apolipoproteins L control cell death triggered by TLR3/TRIF signaling in dendritic cells

Abstract: Additional supporting information may be found in the online version of this article at the publisher's web-site

Cited by 39 publications

References 54 publications

Gene Co-expression Analysis Indicates Potential Pathways and Regulators of Beef Tenderness in Nellore Cattle

Gene Co-expression Analysis Indicates Potential Pathways and Regulators of Beef Tenderness in Nellore Cattle

Immunogenicity of DNA Vaccine against H5N1 Containing Extended Kappa B Site: In Vivo Study in Mice and Chickens

APOL1 Renal Risk Variants: Fertile Soil for HIV-Associated Nephropathy

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