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Yves Pacheco, Alain Calender, Dominique Israël-Biet, Pascal Roy, Serge Lebecque, Vincent Cottin, Diane Bouvry, Hilario Nunes, Pascal Sève, Laurent Pérard, Gilles Devouassoux, Nathalie Freymond, Chahira Khouatra, Benoît Wallaert, Raphaelle Lamy, Mad-Hélénie Elsensohn, Claire Bardel, Dominique Valeyre
BACKGROUND: The occurrence of familial forms of sarcoidosis (OMIM 181100) suggests a genetic predisposition. The involvement of butyrophilin-like 2 (BTNL2) gene (rs2076530 variant) has to be investigated. RESULTS: The study performed independent analyses of BTNL2 polymorphism, clinical phenotypes, and outcomes in familial vs. sporadic presentations in 256 sporadic and 207 familial cases from 140 families. The logistic multivariate model showed that a young age at diagnosis and the combination of lung and skin involvement at diagnosis may distinguish sporadic from familial sarcoidosis (p = 0...
December 3, 2016: Orphanet Journal of Rare Diseases
Rafael Di Marco Barros, Natalie A Roberts, Robin J Dart, Pierre Vantourout, Anett Jandke, Oliver Nussbaumer, Livija Deban, Sara Cipolat, Rosie Hart, Maria Luisa Iannitto, Adam Laing, Bradley Spencer-Dene, Philip East, Deena Gibbons, Peter M Irving, Pablo Pereira, Ulrich Steinhoff, Adrian Hayday
Many body surfaces harbor organ-specific γδ T cell compartments that contribute to tissue integrity. Thus, murine dendritic epidermal T cells (DETCs) uniquely expressing T cell receptor (TCR)-Vγ5 chains protect from cutaneous carcinogens. The DETC repertoire is shaped by Skint1, a butyrophilin-like (Btnl) gene expressed specifically by thymic epithelial cells and suprabasal keratinocytes. However, the generality of this mechanism has remained opaque, since neither Skint1 nor DETCs are evolutionarily conserved...
September 22, 2016: Cell
Adriana Amaro, Federica Parodi, Konrad Diedrich, Giovanna Angelini, Cornelia Götz, Silvia Viaggi, Irena Maric, Domenico Coviello, Maria Pia Pistillo, Anna Morabito, Mario Mandalà, Paola Ghiorzo, Paola Visconti, Marina Gualco, Luca Anselmi, Roberto Puzone, Francesco Lanza, Carlo Mosci, Federica Raggi, Maria Carla Bosco, Luigi Varesio, Michael Zeschnigk, Laura Spano, Paola Queirolo, Ulrich Pfeffer
Importance: Chromosome 6p amplification is associated with more benign behavior for uveal melanomas (UMs) with an otherwise high risk of metastasis conferred by chromosome 3 monosomy. Chromosome 6p contains several members of the B7 family of immune regulator genes, including butyrophilin-like 2 (BTNL2; OMIM, 606000), which is associated with prostate cancer risk and autoimmune diseases. Objective: To investigate the expression and variant allele frequencies of BTNL2, a candidate gene for chromosome 6 amplification, in patients with UM...
October 1, 2016: JAMA Ophthalmology
Cristina Lebrero-Fernández, Anna Bas-Forsberg
Murine Butyrophilin-like (Btnl) 1 and Btnl6 are primarily restricted to intestinal epithelium where they regulate the function of intraepithelial T lymphocytes. We recently demonstrated that Btnl1 and Btnl6 can form an intra-family heterocomplex and that the Btnl1-Btnl6 complex selectively expands Vγ7Vδ4 TCR IELs. To define the regulation of Btnl expression in the small intestine during ontogeny we examined the presence of Btnl1 and Btnl6 in the small bowel of newborn to 4-week-old mice. Although RNA expression of Btnl1 and Btnl6 was detected in the small intestine at day 0, Btnl1 and Btnl6 protein expression was substantially delayed and was not detectable in the intestinal epithelium until the mice reached 2-3 weeks of age...
2016: Scientific Reports
Xiang Tong, Yao Ma, Xundong Niu, Zhipeng Yan, Sitong Liu, Bo Peng, Shifeng Peng, Hong Fan
OBJECTIVE: The butyrophilin-like 2 (BTNL2) G16071A gene polymorphism has been implicated in the susceptibility to granulomatous diseases, but the results were inconclusive. The objective of the current study was to precisely explore the relationship between BTNL2 G16071A gene polymorphism and granulomatous disease susceptibility by the meta-analysis including false-positive report probability (FPRP) test. METHODS: A systematic literature search in the PubMed, Embase, and Wanfang databases, China National Knowledge Internet, and commercial Internet search engines was conducted to identify studies published up to April 1, 2016...
July 2016: Medicine (Baltimore)
Cristina Lebrero-Fernández, Joakim H Bergström, Thaher Pelaseyed, Anna Bas-Forsberg
To date, few molecular conduits mediating the cross-talk between intestinal epithelial cells and intraepithelial lymphocytes (IELs) have been described. We recently showed that butyrophilin-like (Btnl) 1 can attenuate the epithelial response to activated IELs, resulting in reduced production of proinflammatory mediators, such as IL-6 and CXCL1. We here report that like Btnl1, murine Btnl6 expression is primarily confined to the intestinal epithelium. Although Btnl1 can exist in a cell surface-expressed homomeric form, we found that it additionally forms heteromeric complexes with Btnl6, and that the engagement of Btnl1 is a prerequisite for surface expression of Btnl6 on intestinal epithelial cells...
2016: Frontiers in Immunology
Liang Cheng, Rong Zhao, ZhenXiao Jin, Kai Ren, Chao Deng, Shiqiang Yu
BACKGROUND: Dilated cardiomyopathy (DCM) is one type of primary myocardial disease, partly caused by immunity dysfunctions. BTNL2 (butyrophilin-like 2) has already been confirmed to be involved in the etiology of autoimmune disorders and GWAS (genome wide association study) has also identified mutants of a SNP (single nucleotide polymorphism) near BTNL2 could modulate risk of coronary heart disease (also cardiomyopathy). The current study, therefore, was aimed to investigate whether polymorphisms within or around BTNL2 would be correlated with susceptibility to and prognosis of DCM...
2015: International Journal of Clinical and Experimental Pathology
Yanxia Guo, Adele Y Wang
The great success of anti-cytotoxic lymphocyte antigen 4 (CTLA4) and anti-programed cell death protein 1 (PD1) in cancer treatment has encouraged more effort in harnessing the immune response through immunomodulatory molecules in various diseases. The immunoglobulin (Ig) super family comprises the majority of immunomodulatory molecules. Discovery of novel Ig super family members has brought novel insights into the function of different immune cells in tolerance maintenance. In this review, we discuss the function of newly identified B7 family molecules, B7-H4 and V-domain Ig Suppressor of T cell Activation (VISTA), and the butyrophilin/butyrophilin-like family members...
2015: Frontiers in Immunology
Krishanthi S Subramaniam, Emily Spaulding, Emil Ivan, Eugene Mutimura, Ryung S Kim, Xikui Liu, Chen Dong, Catherine M Feintuch, Xingxing Zhang, Kathryn Anastos, Gregoire Lauvau, Johanna P Daily
Plasmodium falciparum infection can result in severe disease that is associated with elevated inflammation and vital organ dysfunction; however, malaria-endemic residents gain protection from lethal outcomes and manifest only mild symptoms during infection. To characterize host responses associated with this more effective antimalarial response, we characterized whole-blood transcriptional profiles in Rwandan adults during a mild malaria episode and compared them with findings from a convalescence sample. We observed transcriptional up-regulation in many pathways, including type I interferon, interferon γ, complement activation, and nitric oxide during malaria infection, which provide benchmarks of mild disease physiology...
October 15, 2015: Journal of Infectious Diseases
Yihua Lin, Jia Wei, Lili Fan, Deyun Cheng
BACKGROUND: Butyrophilin-like 2 (BTNL2) rs2076530 gene polymorphism has been implicated in susceptibility to sarcoidosis. However, results from previous studies are not consistent. To assess the association of BTNL2 polymorphism and sarcoidosis susceptibility, a meta-analysis was performed. METHODS: PubMed, Embase were searched for eligible case-control studies. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. RESULTS: Ten studies involving a total of 3303 cases and 2514 controls were included in this meta-analysis...
2015: PloS One
David A Rhodes, Hung-Chang Chen, Amanda J Price, Anthony H Keeble, Martin S Davey, Leo C James, Matthias Eberl, John Trowsdale
The three butyrophilin BTN3A molecules, BTN3A1, BTN3A2, and BTN3A3, are members of the B7/butyrophilin-like group of Ig superfamily receptors, which modulate the function of T cells. BTN3A1 controls activation of human Vγ9/Vδ2 T cells by direct or indirect presentation of self and nonself phosphoantigens (pAg). We show that the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate binds to the intracellular B30.2 domain of BTN3A1 with an affinity of 1.1 μM, whereas the endogenous pAg isopentenyl pyrophosphate binds with an affinity of 627 μM...
March 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Muhsin Ozdemir, Faruk Saydam, Emel Kurt, Irfan Değirmenci, Tunç Tuncel, Oğuz Cilingir, Hasan Veysi Güneş, Sevilhan Artan
BACKGROUND/AIM: Sarcoidosis is a complex, multifactorial immune disorder with unknown etiology. A single nucleotide polymorphism (G→A, rs2076530) in the butyrophilin-like 2 (BTNL2) gene results in a truncating protein formation. It has been previously reported that this variation may be a risk factor for sarcoidosis in certain ethnic groups. This study was conducted to determine whether there is any genetic predisposition for the BTNL2 rs2076530 polymorphism in the 329-bp region in Turkish patients with sarcoidosis...
2014: Turkish Journal of Medical Sciences
Chao Yang, Liping Pan, Li Zhang, Xiaopan Wu, Xilin Zhu, Bingyu Yan, Aiqiang Xu, Hui Li, Ying Liu
No response to hepatitis B vaccination is a complex phenomenon, which is induced by the combinations of environmental and genetic factors. The aim of the study was to investigate the association between the polymorphisms of the butyrophilin-like 2 (BTNL2) gene and the immune response to hepatitis B vaccination in a Chinese Han population. A total of 7 single nucleotide polymorphisms in the BTNL2 gene were analyzed in 566 non-responders and 1,040 high-responders to hepatitis B vaccination. The alleles T, T, C, A, G of rs3763316, rs3763311, rs9268494, rs3806156, and rs2076530 were associated with no response to hepatitis B vaccination (P = 0...
July 2014: Journal of Medical Virology
Andrei I Chapoval, Glennda Smithson, Linda Brunick, Mehdi Mesri, Ferenc L Boldog, David Andrew, Nikolai V Khramtsov, Elena A Feshchenko, Gary C Starling, Peter S Mezes
The role of the B7 family molecules in the regulation of the immune response is well documented. A large body of experimental evidence indicates that costimulatory molecules such as B7-1, B7-2, B7-DC, B7-H1, B7-H2, B7-H3 and B7-H4 are critical for initiation, maintenance and down-regulation of the immune response. However the immunological function of butyrophilin (BTN)-like molecules, which are a part of the expanded B7 family, is not known. Here, we demonstrate that the extracellular portion of human BTNL8 can augment Ag-induced activation of T lymphocytes...
December 2013: Molecular Immunology
Liesel M Fitzgerald, Akash Kumar, Evan A Boyle, Yuzheng Zhang, Laura M McIntosh, Suzanne Kolb, Marni Stott-Miller, Tiffany Smith, Danielle M Karyadi, Elaine A Ostrander, Li Hsu, Jay Shendure, Janet L Stanford
BACKGROUND: Rare, inherited mutations account for 5% to 10% of all prostate cancer cases. However, to date, few causative mutations have been identified. METHODS: To identify rare mutations for prostate cancer, we conducted whole-exome sequencing (WES) in multiple kindreds (n = 91) from 19 hereditary prostate cancer (HPC) families characterized by aggressive or early-onset phenotypes. Candidate variants (n = 130) identified through family- and bioinformatics-based filtering of WES data were then genotyped in an independent set of 270 HPC families (n = 819 prostate cancer cases; n = 496 unaffected relatives) for replication...
September 2013: Cancer Epidemiology, Biomarkers & Prevention
Johanna Aigner, Sergi Villatoro, Raquel Rabionet, Jaume Roquer, Jordi Jiménez-Conde, Eulàlia Martí, Xavier Estivill
BACKGROUND: The Butyrophilin-like (BTNL) proteins are likely to play an important role in inflammation and immune response. Like the B7 protein family, many human and murine BTNL members have been shown to control T lymphocytes response, and polymorphisms in human BTNL2 have been linked to several inflammatory diseases, such as pulmonary sarcoidosis, inflammatory bowel disease and neonatal lupus. RESULTS: In this study we provide a comprehensive population, genomic and transcriptomic analysis of a 56-kb deletion copy number variant (CNV), located within two segmental duplications of two genes belonging to the BTNL family, namely BTNL8 and BTNL3...
July 6, 2013: BMC Genetics
Yinhua Huang, Yingrui Li, David W Burt, Hualan Chen, Yong Zhang, Wubin Qian, Heebal Kim, Shangquan Gan, Yiqiang Zhao, Jianwen Li, Kang Yi, Huapeng Feng, Pengyang Zhu, Bo Li, Qiuyue Liu, Suan Fairley, Katharine E Magor, Zhenlin Du, Xiaoxiang Hu, Laurie Goodman, Hakim Tafer, Alain Vignal, Taeheon Lee, Kyu-Won Kim, Zheya Sheng, Yang An, Steve Searle, Javier Herrero, Martien A M Groenen, Richard P M A Crooijmans, Thomas Faraut, Qingle Cai, Robert G Webster, Jerry R Aldridge, Wesley C Warren, Sebastian Bartschat, Stephanie Kehr, Manja Marz, Peter F Stadler, Jacqueline Smith, Robert H S Kraus, Yaofeng Zhao, Liming Ren, Jing Fei, Mireille Morisson, Pete Kaiser, Darren K Griffin, Man Rao, Frederique Pitel, Jun Wang, Ning Li
The duck (Anas platyrhynchos) is one of the principal natural hosts of influenza A viruses. We present the duck genome sequence and perform deep transcriptome analyses to investigate immune-related genes. Our data indicate that the duck possesses a contractive immune gene repertoire, as in chicken and zebra finch, and this repertoire has been shaped through lineage-specific duplications. We identify genes that are responsive to influenza A viruses using the lung transcriptomes of control ducks and ones that were infected with either a highly pathogenic (A/duck/Hubei/49/05) or a weakly pathogenic (A/goose/Hubei/65/05) H5N1 virus...
July 2013: Nature Genetics
Shigeki Mitsunaga, Kazuyoshi Hosomichi, Yuko Okudaira, Hirofumi Nakaoka, Nanae Kunii, Yasuo Suzuki, Masataka Kuwana, Shinji Sato, Yuko Kaneko, Yasuhiko Homma, Koichi Kashiwase, Fumihiro Azuma, Jerzy K Kulski, Ituro Inoue, Hidetoshi Inoko
The butyrophilin-like protein 2 gene (BTNL2) within the class III region of the major histocompatibility complex genomic region was identified as a rheumatoid arthritis (RA) susceptibility gene by exome sequencing (19 RA cases) with stepwise filtering analysis, and then validated by Sanger sequencing and association analysis using 432 cases and 432 controls. Logistic regression of the Sanger-sequenced single-nucleotide variants in an association study of 432 cases and 432 controls showed that 12 non-synonymous single-nucleotide polymorphisms (SNPs) in BTNL2 were significantly associated with RA...
April 2013: Journal of Human Genetics
Ryan M Swanson, Marc A Gavin, Sabine S Escobar, James B Rottman, Brian P Lipsky, Shishir Dube, Li Li, Jeannette Bigler, Martin Wolfson, Heather A Arnett, Joanne L Viney
Naive T cell activation involves at least two signals from an APC, one through the TCR via interaction with peptide-MHC complexes and a second through ligation of CD28 with B7 ligands. Following activation, T cells upregulate a host of other membrane-bound costimulatory molecules that can either promote or inhibit further T cell maturation and proliferation. In some cases, it is necessary to attenuate T cell activation to prevent deleterious inflammation, and inhibitory members of the B7/butyrophilin family of ligands have evolved to balance the strong stimuli the activating B7 ligands confer...
March 1, 2013: Journal of Immunology: Official Journal of the American Association of Immunologists
António Morais, Bruno Lima, Maria José Peixoto, Helena Alves, Agostinho Marques, Luís Delgado
A functional polymorphism within butyrophilin-like 2 (BTNL2) gene has been described as a potential risk factor for sarcoidosis. The association between chronicity and the rs2076530 SNP A allele has also been reported. This study evaluates the BTNL2 rs2076530 G/A allele associations with sarcoidosis susceptibility and disease evolution in a Portuguese cohort of patients. A case-control study of 151 patients and 150 controls was performed. Allele frequencies were compared with Chi-square test in a univariate analysis and with logistic regression in a multivariate analysis...
December 2012: Respiratory Medicine
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