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Pierre Vantourout, Adam Laing, Martin J Woodward, Iva Zlatareva, Luis Apolonia, Andrew W Jones, Ambrosius P Snijders, Michael H Malim, Adrian C Hayday
The long-held view that gamma delta (γδ) T cells in mice and humans are fundamentally dissimilar, as are γδ cells in blood and peripheral tissues, has been challenged by emerging evidence of the cells' regulation by butyrophilin (BTN) and butyrophilin-like (BTNL) molecules. Thus, murine Btnl1 and the related gene, Skint1 , mediate T cell receptor (TCR)-dependent selection of murine intraepithelial γδ T cell repertoires in gut and skin, respectively; BTNL3 and BTNL8 are TCR-dependent regulators of human gut γδ cells; and BTN3A1 is essential for TCR-dependent activation of human peripheral blood Vγ9Vδ2+ T cells...
January 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
Cristina Lebrero-Fernández, Ulf Alexander Wenzel, Paulina Akeus, Ying Wang, Hans Strid, Magnus Simrén, Bengt Gustavsson, Lars G Börjesson, Susanna L Cardell, Lena Öhman, Marianne Quiding-Järbrink, Anna Bas-Forsberg
Several Butyrophilin (BTN) and Btn-like (BTNL) molecules control T lymphocyte responses, and are genetically associated with inflammatory disorders and cancer. In this study, we present a comprehensive expression analysis of human and murine BTN and BTNL genes in conditions associated with intestinal inflammation and cancer. Using real-time PCR, expression of human BTN and BTNL genes was analyzed in samples from patients with ulcerative colitis, irritable bowel syndrome, and colon tumors. Expression of murine Btn and Btnl genes was examined in mouse models of spontaneous colitis (Muc2(-/-)) and intestinal tumorigenesis (Apc(Min/+))...
June 2016: Immunity, Inflammation and Disease
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
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
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
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
Lucie Abeler-Dörner, Mahima Swamy, Gareth Williams, Adrian C Hayday, Anna Bas
Butyrophilins (Btns) and butyrophilin-like (Btnl) molecules are emerging as novel regulators of immune responses in mice and humans. Several clues point to their probable importance: many of the genes are located within the MHC; they are structurally related to B7-co-stimulatory molecules; they are functionally implicated in T cell inhibition and in the modulation of epithelial cell-T cell interactions; and they are genetically associated with inflammatory diseases. Nonetheless, initial immersion into the current literature can uncover confusion over even basic information such as gene names and expression patterns, and seemingly conflicting data regarding the biological activities of different family members...
January 2012: Trends in Immunology
Anna Bas, Mahima Swamy, Lucie Abeler-Dörner, Gareth Williams, Dick J Pang, Susannah D Barbee, Adrian C Hayday
Although local regulation of T-cell responses by epithelial cells is increasingly viewed as important, few molecules mediating such regulation have been identified. Skint1, a recently identified member of the Ig-supergene family expressed by thymic epithelial cells and keratinocytes, specifies the murine epidermal intraepithelial lymphocyte (IEL) repertoire. Investigating whether Skint1-related molecules might regulate IEL in other compartments, this study focuses on buytrophilin-like 1 (Btnl1), which is conspicuously similar to Skint1 and primarily restricted to small intestinal epithelium...
March 15, 2011: Proceedings of the National Academy of Sciences of the United States of America
Tomohide Yamazaki, Iñigo Goya, Daniel Graf, Suzanne Craig, Natalia Martin-Orozco, Chen Dong
The costimulatory molecules in the B7-CD28 families are important in the regulation of T cell activation and tolerance. The butyrophilin family of proteins shares sequence and structure homology with B7 family molecules; however, the function of the butyrophilin family in the immune system has not been defined. In this study, we performed an analysis on multiple butyrophilin molecules and found that butyrophilin-like (BTNL)1 molecule functions to dampen T cell activation. BTNL1 mRNA was broadly expressed, but its protein was only found in APCs and not T cells...
November 15, 2010: Journal of Immunology: Official Journal of the American Association of Immunologists
Anne Averdam, Christiane Kuschal, Nicole Otto, Nico Westphal, Christian Roos, Richard Reinhardt, Lutz Walter
We here report the genomic organisation of the grey mouse lemur (Microcebus murinus) MHC class II DQ and DR region based on BAC clone analysis. The sequenced Mimu-MHC haplotype spans 343 kb and encompasses the genes TAP2, DOB, DQB, DQA, DRB, DRA, BTNL2 and a further BTNL gene. The DQ and DR genes of this haplotype are not duplicated. Mimu-DOB is not transcribed and represents a pseudogene due to deletions and premature stop codons. Analysis of BAC clone DNA, a cDNA sample and eight genomic DNA samples suggests that Mimu-DRB, Mimu-DQA and Mimu-DQB are highly polymorphic with the majority of peptide-binding residues being affected by polymorphisms...
February 2011: Immunogenetics
K Liu, P Zhang, J Gao, H Liu, G Li, Z Qiu, Y Zhang, J Ren, P Tan, R Z Ma
A 184 kb gap in an ovine MHC physical map was successfully closed by identification of two overlapping clones (304C7 and 222G18) from a Chinese fine wool merino sheep BAC library. The location and tiling path of the two clones were confirmed by BAC-end sequencing and PCR amplification of loci in overlapping regions. Full-length sequencing of the clones identified 13 novel ovine genes in the gap between loci Notch4 and Btnl2, and eight of them belonging to the Butyrophilin-like (Btn-like or Btnl) gene family...
April 2011: Animal Genetics
C Renard, E Hart, H Sehra, H Beasley, P Coggill, K Howe, J Harrow, J Gilbert, S Sims, J Rogers, A Ando, A Shigenari, T Shiina, H Inoko, P Chardon, S Beck
We describe the generation and analysis of an integrated sequence map of a 2.4-Mb region of pig chromosome 7, comprising the classical class I region, the extended and classical class II regions, and the class III region of the major histocompatibility complex (MHC), also known as swine leukocyte antigen (SLA) complex. We have identified and manually annotated 151 loci, of which 121 are known genes (predicted to be functional), 18 are pseudogenes, 8 are novel CDS loci, 3 are novel transcripts, and 1 is a putative gene...
July 2006: Genomics
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