Butyrophilins: an emerging family of immune regulators

Abeler-Dörner, Lucie; Swamy, Mahima; Williams, Gareth; Hayday, Adrian; Bas, Anna

doi:10.1016/j.it.2011.09.007

Cited by 120 publications

(121 citation statements)

References 39 publications

Supporting

Mentioning

120

Contrasting

Order By: Relevance

“…Conversely, reduced levels of BTNL9 suggest a reduced ability of the mutant virus to control T cell activation (Table 4). The butyrophilin-like family encodes transmembrane glycoproteins with roles in immune coregulation and antigen presentation, and some of them are functionally implicated in T cell inhibition and in the modulation of epithelial cell-T cell interactions (64)(65)(66).…”

Section: Discussionmentioning

confidence: 99%

A 2.5-Kilobase Deletion Containing a Cluster of Nine MicroRNAs in the Latency-Associated-Transcript Locus of the Pseudorabies Virus Affects the Host Response of Porcine Trigeminal Ganglia during Established Latency

Mahjoub

Dhorne–Pollet

Fuchs

et al. 2015

J Virol

View full text Add to dashboard Cite

The alphaherpesvirus pseudorabies virus (PrV) establishes latency primarily in neurons of trigeminal ganglia when only the transcription of the latency-associated transcript (LAT) locus is detected. Eleven microRNAs (miRNAs) cluster within the LAT, suggesting a role in establishment and/or maintenance of latency. We generated a mutant (M) PrV deleted of nine miRNA genes which displayed properties that were almost identical to those of the parental PrV wild type (WT) during propagation in vitro. IMPORTANCEThis study provides a thorough reference on the establishment of latency by PrV in its natural host, the pig. Our results corroborate the evidence obtained from the study of several LAT mutants of other alphaherpesviruses encoding miRNAs from their LAT regions. Neither PrV miRNA expression nor high LLT expression levels are essential to achieve latency in trigeminal ganglia. Once latency is established by PrV, the only remarkable differences are found in the pattern of host response. This indicates that, as in herpes simplex virus, LAT functions as an immune evasion locus. P seudorabies virus (PrV) is a porcine alphaherpesvirus. The genome of PrV is more than 142 kb in size and is characterized by the presence of 70 different coding genes plus the latency-associated transcript (LAT) locus (1, 2). PrV is the etiological agent of Aujeszky's disease, causing neurological, respiratory, and reproductive disease in the pig, its natural host. Despite successful vaccination campaigns and eradication of the virus from various countries, pseudorabies outbreaks still occur in swine populations worldwide, as recently reported from China (3). Because latent infection persists for lifetime after recovery from acute disease, pigs latently infected by PrV are a constant danger for virus reactivation, shedding, and spread in susceptible populations (4-6).A particular feature of herpesviruses is their ability to establish and maintain latent infections in which the virus genome circularizes and persists as an episome. As for other alphaherpesviruses, neurons in the trigeminal ganglia are the primary site of PrV latency (7). Over this period, transcription of viral lytic genes is repressed and transcription of the viral genome is restricted to the LAT locus overlapping the internal repeat sequence (IR) (8-10).RNAs of multiple sizes are transcribed from the strand opposite that encoding EP0 and IE180, which can be detected in infected Citation Mahjoub N, Dhorne-Pollet S, Fuchs W, Endale Ahanda M-L, Lange E, Klupp B, Arya A, Loveland JE, Lefevre F, Mettenleiter TC, Giuffra E. 2015. A 2.5-kilobase deletion containing a cluster of nine microRNAs in the latencyassociated-transcript locus of the pseudorabies virus affects the host response of porcine trigeminal ganglia during established latency.

show abstract

Section: Discussionmentioning

confidence: 99%

A 2.5-Kilobase Deletion Containing a Cluster of Nine MicroRNAs in the Latency-Associated-Transcript Locus of the Pseudorabies Virus Affects the Host Response of Porcine Trigeminal Ganglia during Established Latency

Mahjoub

Dhorne–Pollet

Fuchs

et al. 2015

J Virol

View full text Add to dashboard Cite

show abstract

“…Tripartite motif (TRIM) genes are often found in proximity to butyrophilin loci, suggesting a common evolutionary link. Several published reviews cover these general aspects of the structure, genomic organization, and expression of the butyrophilins (6)(7)(8).…”

Section: Immunogeneticsmentioning

confidence: 99%

“…Human immunoglobulin (Ig) superfamily receptor proteins of the butyrophilin and butyrophilin-like families, termed BTN and BTNL, have also been recognized as potentially important immune modulators (5)(6)(7)(8). The Ig domains from butyrophilins exhibit some structural features of the B7 family of coreceptors, such as CD80 and CD86, ICOS-L, and PD-L1 (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Regulation of Immunity by Butyrophilins

Rhodes

Reith

Trowsdale

2016

Annu. Rev. Immunol.

134

137

View full text Add to dashboard Cite

Butyrophilin molecules (commonly contracted to BTN), collectively take their name from the eponymous protein in cow's milk. They are considered to be members of the B7 family of costimulatory receptors, which includes B7.1 (CD80), B7.2 (CD86), and related molecules, such as PD-L1 (B7-H1, CD274), ICOS-L (CD275), and B7-H3 (CD276). These coreceptors modulate T cell responses upon antigen presentation by major histocompatibility complex and cognate αβ T cell receptor engagement. Molecules such as BTN3A1 (CD277), myelin oligodendrocyte glycoprotein, and mouse Skint1 and Btnl2, all members of the butyrophilin family, show greater structural and functional diversity than the canonical B7 receptors. Some butyrophilins mediate complex interactions between antigen-presenting cells and conventional αβ T cells, and others regulate the immune responses of specific γδ T cell subsets by mechanisms that have characteristics of both innate and adaptive immunity.

show abstract

“…BTNL2 is located in close proximity to the HLA-DRB1 gene (≈200 kb) and has been associated with inflammatory autoimmune diseases and with lipid levels. [35][36][37] BTNL2 is thought to encode a negative costimulatory-receptor for T cells, possibly inhibiting both T cell proliferation and interleukin-2 production. 38 The truncating mutation of BTNL2 seen in sarcoidosis has been suspected to downregulate its function, leading to inappropriate inflammation.…”

Section: Discussionmentioning

confidence: 99%

Novel 6p21.3 Risk Haplotype Predisposes to Acute Coronary Syndrome

Sinisalo

Vlachopoulou

Marchesani

et al. 2016

Circ Cardiovasc Genet

View full text Add to dashboard Cite

Background-The HLA-DRB1*01 allele of the human leukocyte antigen has been associated with acute coronary syndrome.Genome-wide association studies have revealed associations with human leukocyte antigen and non-human leukocyte antigen genes of 3 major histocompatibility complex gene classes but not at allelic level. Methods and Results-We conducted a large-scale genetic analysis on a case-control cohort comprising 5376 acute coronary syndrome cases and 4852 unrelated controls from 4 populations of 2 European countries. We analyzed the risk candidate allele of HLA-DRB1*01 by genomic real-time polymerase chain reaction together with high-density single nucleotide polymorphisms of the major histocompatibility complex to precisely identify risk loci for acute coronary syndrome with effective clinical implications. We found a risk haplotype for the disease containing single nucleotide polymorphisms from BTNL2 and HLA-DRA genes and the HLA-DRB1*01 allele. The association of the haplotype appeared in 3 of the 4 populations, and the direction of the effect was consistent in the fourth. Coronary samples from subjects homozygous for the disease-associated haplotype showed higher BTNL2 mRNA levels (r=0.760; P<0.00001).We localized, with immunofluorescence staining, BTNL2 in CD68-positive macrophages of the coronary artery plaques. In homozygous cases, BTNL2 blocking, in T-cell stimulation assays, enhanced CD4 10,11 This may explain why the HLA-DRB1*01 association has emerged only in studies with direct HLA allele typing, but in no GWA studies.2,4 HLA-DRB1*01 may play a role in promoting coronary artery disease by affecting antigen presentation.12 Presentation of peptide fragments of oxidized low-density lipoprotein cholesterol may connect the cholesterol pathway to inflammation and immunology in atherosclerosis progression. Clinical Perspective on p 63Because of the promising results from previous GWA and candidate gene studies and the fact that the MHC contains many genes with putative immune functions, we hypothesized that analysis of other MHC genes using high-density SNPs stratified according to the HLA-DRB1*01 allele will show novel associations with acute coronary syndrome (ACS) with effective clinical implications. Materials and Methods Patient PopulationsOur entire study comprised 1 discovery population (from Finland) and 3 replication populations (I and II from Finland and III from Spain) for a total of 5376 cases and 4852 control subjects. The discovery population included 2090 ACS cases. 13 Replication population I included 742 cases either with ST-elevation myocardial infarction or non-ST-elevation myocardial infarction.14 Replication population II included 762 either ST-elevation myocardial infarction or non-STelevation myocardial infarction cases. 15 Replication population III included 1768 first myocardial infarction cases. 16,17 Control subjects for discovery and replication populations I and II were selected from The National FINRISK Study (FINRISK) 1992(FINRISK) , 1997(FINRISK) , 2002(FINRISK) , and ...

show abstract

Butyrophilins: an emerging family of immune regulators

Cited by 120 publications

References 39 publications

A 2.5-Kilobase Deletion Containing a Cluster of Nine MicroRNAs in the Latency-Associated-Transcript Locus of the Pseudorabies Virus Affects the Host Response of Porcine Trigeminal Ganglia during Established Latency

A 2.5-Kilobase Deletion Containing a Cluster of Nine MicroRNAs in the Latency-Associated-Transcript Locus of the Pseudorabies Virus Affects the Host Response of Porcine Trigeminal Ganglia during Established Latency

Regulation of Immunity by Butyrophilins

Novel 6p21.3 Risk Haplotype Predisposes to Acute Coronary Syndrome

Contact Info

Product

Resources

About