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Your search keyword '"Bossini-Castillo L"' showing total 7 results
Start Over Author "Bossini-Castillo L" Publisher bmj publishing group
7 results on '"Bossini-Castillo L"'

1. Histone modifications underlie monocyte dysregulation in patients with systemic sclerosis, underlining the treatment potential of epigenetic targeting

Author

Van Der Kroef, M., Castellucci, M., Mokry, M., Cossu, M., Garonzi, M., Bossini-Castillo, L., Chouri, E., Wichers, C.G.K., Beretta, L., Trombetta, E., Silva-Cardoso, S., Vazirpanah, N., Carvalheiro, T., Angiolilli, C., Bekker, C.P.J., Affandi, A.J., Reedquist, K.A., Bonte-Mineur, F., Zirkzee, E.J.M., Bazzoni, F., Radstake, T.R.D.J., and Rossato, M.

Subjects
0301 basic medicine, Male, systemic sclerosis, Biochemistry, Epigenesis, Genetic, Histones, 0302 clinical medicine, epigenetic targeting, Medicine, Immunology and Allergy, histone modification, Molecular Targeted Therapy, biology, Monocyte homeostasis, Azepines, Middle Aged, Chromatin, Histone Code, Histone, STAT1 Transcription Factor, Female, monocytes, Adult, Immunology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Rheumatology, Humans, Epigenetics, Aged, 030203 arthritis & rheumatology, Scleroderma, Systemic, epigenetics, business.industry, Biochemistry, Genetics and Molecular Biology(all), Gene Expression Profiling, Interferon-alpha, Promoter, STAT2 Transcription Factor, Triazoles, Chromatin Assembly and Disassembly, Bromodomain, 030104 developmental biology, Gene Expression Regulation, Case-Control Studies, Cancer research, biology.protein, H3K4me3, business, Chromatin immunoprecipitation, Genetics and Molecular Biology(all)
Abstract

Background and objectiveSystemic sclerosis (SSc) is a severe autoimmune disease, in which the pathogenesis is dependent on both genetic and epigenetic factors. Altered gene expression in SSc monocytes, particularly of interferon (IFN)-responsive genes, suggests their involvement in SSc development. We investigated the correlation between epigenetic histone marks and gene expression in SSc monocytes.MethodsChromatin immunoprecipitation followed by sequencing (ChIPseq) for histone marks H3K4me3 and H3K27ac was performed on monocytes of nine healthy controls and 14 patients with SSc. RNA sequencing was performed in parallel to identify aberrantly expressed genes and their correlation with the levels of H3K4me3 and H3K27ac located nearby their transcription start sites. ChIP-qPCR assays were used to verify the role of bromodomain proteins, H3K27ac and STATs on IFN-responsive gene expression.Results1046 and 534 genomic loci showed aberrant H3K4me3 and H3K27ac marks, respectively, in SSc monocytes. The expression of 381 genes was directly and significantly proportional to the levels of such chromatin marks present near their transcription start site. Genes correlated to altered histone marks were enriched for immune, IFN and antiviral pathways and presented with recurrent binding sites for IRF and STAT transcription factors at their promoters. IFNα induced the binding of STAT1 and STAT2 at the promoter of two of these genes, while blocking acetylation readers using the bromodomain BET family inhibitor JQ1 suppressed their expression.ConclusionSSc monocytes have altered chromatin marks correlating with their IFN signature. Enzymes modulating these reversible marks may provide interesting therapeutic targets to restore monocyte homeostasis to treat or even prevent SSc.

Published
2019

2. Low RUNX3 expression alters dendritic cell function in patients with systemic sclerosis and contributes to enhanced fibrosis

Author

Affandi, A.J., Carvalheiro, T., Ottria, A., Broen, J.C.A., Bossini-Castillo, L., Tieland, R.G., Bon, L.V., Chouri, E., Rossato, M., Mertens, J.S., García, S., Pandit, A., De Kroon, L.M.G., Christmann, R.B., Martín, J., Van Roon, J.A.G., Radstake, Timothy R. D. J., Marut, W., Affandi, A.J., Carvalheiro, T., Ottria, A., Broen, J.C.A., Bossini-Castillo, L., Tieland, R.G., Bon, L.V., Chouri, E., Rossato, M., Mertens, J.S., García, S., Pandit, A., De Kroon, L.M.G., Christmann, R.B., Martín, J., Van Roon, J.A.G., Radstake, Timothy R. D. J., and Marut, W.

Abstract

Objectives: Systemic sclerosis (SSc) is an autoimmune disease with unknown pathogenesis manifested by inflammation, vasculopathy and fibrosis in skin and internal organs. Type I interferon signature found in SSc propelled us to study plasmacytoid dendritic cells (pDCs) in this disease. We aimed to identify candidate pathways underlying pDC aberrancies in SSc and to validate its function on pDC biology. Methods: In total, 1193 patients with SSc were compared with 1387 healthy donors and 8 patients with localised scleroderma. PCR-based transcription factor profiling and methylation status analyses, single nucleotide polymorphism genotyping by sequencing and flow cytometry analysis were performed in pDCs isolated from the circulation of healthy controls or patients with SSc. pDCs were also cultured under hypoxia, inhibitors of methylation and hypoxia-inducible factors and runt-related transcription factor 3 (RUNX3) levels were determined. To study Runx3 function, Itgax-Cre:Runx3 mice were used in in vitro functional assay and bleomycin-induced SSc skin inflammation and fibrosis model. Results: Here, we show downregulation of transcription factor RUNX3 in SSc pDCs. A higher methylation status of the RUNX3 gene, which is associated with polymorphism rs6672420, correlates with lower RUNX3 expression and SSc susceptibility. Hypoxia is another factor that decreases RUNX3 level in pDC. Mouse pDCs deficient of Runx3 show enhanced maturation markers on CpG stimulation. In vivo, deletion of Runx3 in dendritic cell leads to spontaneous induction of skin fibrosis in untreated mice and increased severity of bleomycin-induced skin fibrosis. Conclusions: We show at least two pathways potentially causing low RUNX3 level in SSc pDCs, and we demonstrate the detrimental effect of loss of Runx3 in SSc model further underscoring the role of pDCs in this disease.

Published
2019

3. A MIF PROMOTER POLYMORPHISM IS ASSOCIATED WITH THE SUSCEPTIBILITY TO PULMONARY ARTERIAL HYPERTENSION IN DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS PATIENTS

Author

Lopez-Isac, E., Bossini-Castillo, L., Campillo-Davo, D., Carmona, F. D., Simeon, C. P., Carreira, P., Callejas-Rubio, J. L., Castellvi, I., Fernandez-Nebro, A., Rodriguez-Rodriguez, L., Rubio Rivas, M., Garcia Hernandez, F. J., Madronero, A. B., Beretta, L., Santaniello, A., Lunardi, C., Airo, P., Hoffmann-Vold, A-M., Kreuter, A., Riemekasten, G., Witte, T., Hunzelmann, N., Vonk, M. C., Voskuyl, A. E., Bouwstra, J. D. V., Shiels, P., Herrick, A., Worthington, J., Radstake, T. R. D. J., Martin, J., Lopez-Isac, E., Bossini-Castillo, L., Campillo-Davo, D., Carmona, F. D., Simeon, C. P., Carreira, P., Callejas-Rubio, J. L., Castellvi, I., Fernandez-Nebro, A., Rodriguez-Rodriguez, L., Rubio Rivas, M., Garcia Hernandez, F. J., Madronero, A. B., Beretta, L., Santaniello, A., Lunardi, C., Airo, P., Hoffmann-Vold, A-M., Kreuter, A., Riemekasten, G., Witte, T., Hunzelmann, N., Vonk, M. C., Voskuyl, A. E., Bouwstra, J. D. V., Shiels, P., Herrick, A., Worthington, J., Radstake, T. R. D. J., and Martin, J.

Published
2017

4. A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides

Author

Bossini-Castillo, L., de Kovel, C., Kallberg, H., van 't Slot, R., Italiaander, A., Coenen, M., Tak, P. P., Posthumus, M. D., Wijmenga, C., Huizinga, T., van der Helm-van Mil, A. H. M., Stoeken-Rijsbergen, G., Rodriguez-Rodriguez, Luis, Balsa, Alejandro, Gonzalez-Alvaro, Isidoro, Angel Gonzalez-Gay, Miguel, Gomez-Vaquero, Carmen, Franke, B., Vermeulen, S., van der Horst-Bruinsma, I. E., Dijkmans, B. A. C., Wolbink, G. J., Ophoff, R. A., Maehlen, M. T., van Riel, P., Merriman, M., Klareskog, L., Lie, B. A., Merriman, T., Crusius, J. B. A., Brouwer, E., Martin, J., de Vries, N., Toes, R., Padyukov, L., Koeleman, B. P. C., LifeLines Cohort Study, Bossini-Castillo, L., de Kovel, C., Kallberg, H., van 't Slot, R., Italiaander, A., Coenen, M., Tak, P. P., Posthumus, M. D., Wijmenga, C., Huizinga, T., van der Helm-van Mil, A. H. M., Stoeken-Rijsbergen, G., Rodriguez-Rodriguez, Luis, Balsa, Alejandro, Gonzalez-Alvaro, Isidoro, Angel Gonzalez-Gay, Miguel, Gomez-Vaquero, Carmen, Franke, B., Vermeulen, S., van der Horst-Bruinsma, I. E., Dijkmans, B. A. C., Wolbink, G. J., Ophoff, R. A., Maehlen, M. T., van Riel, P., Merriman, M., Klareskog, L., Lie, B. A., Merriman, T., Crusius, J. B. A., Brouwer, E., Martin, J., de Vries, N., Toes, R., Padyukov, L., Koeleman, B. P. C., and LifeLines Cohort Study

Published
2015

5. A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides

Author

Genetica Groep Koeleman, Hersenen-Bedrijfsvoering, MMB, Child Health, Bossini-Castillo, L., de Kovel, C., Kallberg, H., van 't Slot, R., Italiaander, A., Coenen, M., Tak, P. P., Posthumus, M. D., Wijmenga, C., Huizinga, T., van der Helm-van Mil, A. H. M., Stoeken-Rijsbergen, G., Rodriguez-Rodriguez, Luis, Balsa, Alejandro, Gonzalez-Alvaro, Isidoro, Angel Gonzalez-Gay, Miguel, Gomez-Vaquero, Carmen, Franke, B., Vermeulen, S., van der Horst-Bruinsma, I. E., Dijkmans, B. A. C., Wolbink, G. J., Ophoff, R. A., Maehlen, M. T., van Riel, P., Merriman, M., Klareskog, L., Lie, B. A., Merriman, T., Crusius, J. B. A., Brouwer, E., Martin, J., de Vries, N., Toes, R., Padyukov, L., Koeleman, B. P. C., LifeLines Cohort Study, Genetica Groep Koeleman, Hersenen-Bedrijfsvoering, MMB, Child Health, Bossini-Castillo, L., de Kovel, C., Kallberg, H., van 't Slot, R., Italiaander, A., Coenen, M., Tak, P. P., Posthumus, M. D., Wijmenga, C., Huizinga, T., van der Helm-van Mil, A. H. M., Stoeken-Rijsbergen, G., Rodriguez-Rodriguez, Luis, Balsa, Alejandro, Gonzalez-Alvaro, Isidoro, Angel Gonzalez-Gay, Miguel, Gomez-Vaquero, Carmen, Franke, B., Vermeulen, S., van der Horst-Bruinsma, I. E., Dijkmans, B. A. C., Wolbink, G. J., Ophoff, R. A., Maehlen, M. T., van Riel, P., Merriman, M., Klareskog, L., Lie, B. A., Merriman, T., Crusius, J. B. A., Brouwer, E., Martin, J., de Vries, N., Toes, R., Padyukov, L., Koeleman, B. P. C., and LifeLines Cohort Study

Published
2015

7. A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort.

Author

Bossini-Castillo, L., Broen, Jasper C., Simeón, Carmen P., Beretta, L., Vonk, Madelon C., Ortego-Centeno, N., Espinosa, Gerard, Carreira, P., Camps, M. T., Navarrete, N., González-Escribano, María Francisca, Vicente, Esther, Rodríguez-Rodríguez, Luis, Tolosa, Carlos, Román-Ivorra, J. A., Gómez-Gracía, I., García-Hernández, Francisco José, Castellví, I., Gallego, María, Fernández-Nebro, Antonio, García-Portales, Rosa, Egurbide, M. V., Fonollosa, V., García de la Peña, P., Pros, A., González-Gay, M. A., Hesselstrand, R., Riemekasten, G., Witte, Torsten, Coenen, M. J., Koeleman, B. P., Houssiau, F., Smith, V., Keyser, F. de, Westhovens, R., Langhe, E. de, Voskuyl, Alexandre E., Schuerwegh, A. J., Chee, M. M., Madhok, R., Shiels, Paul G., Fonseca, C., Denton, C., Claes, K., Padyukov, Leonid, Nordin, A., Palm, Øyvind, Lie, B. A., Airó, Paolo, Scorza, R., Laar, Jacob M. van, Hunzelmann, Nicolas, Kreuter, A., Herrick, A., Worthington, J., Radstake, T. R., Martín, J., Rueda, B., Bossini-Castillo, L., Broen, Jasper C., Simeón, Carmen P., Beretta, L., Vonk, Madelon C., Ortego-Centeno, N., Espinosa, Gerard, Carreira, P., Camps, M. T., Navarrete, N., González-Escribano, María Francisca, Vicente, Esther, Rodríguez-Rodríguez, Luis, Tolosa, Carlos, Román-Ivorra, J. A., Gómez-Gracía, I., García-Hernández, Francisco José, Castellví, I., Gallego, María, Fernández-Nebro, Antonio, García-Portales, Rosa, Egurbide, M. V., Fonollosa, V., García de la Peña, P., Pros, A., González-Gay, M. A., Hesselstrand, R., Riemekasten, G., Witte, Torsten, Coenen, M. J., Koeleman, B. P., Houssiau, F., Smith, V., Keyser, F. de, Westhovens, R., Langhe, E. de, Voskuyl, Alexandre E., Schuerwegh, A. J., Chee, M. M., Madhok, R., Shiels, Paul G., Fonseca, C., Denton, C., Claes, K., Padyukov, Leonid, Nordin, A., Palm, Øyvind, Lie, B. A., Airó, Paolo, Scorza, R., Laar, Jacob M. van, Hunzelmann, Nicolas, Kreuter, A., Herrick, A., Worthington, J., Radstake, T. R., Martín, J., and Rueda, B.

Abstract

Objectives: The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features. Methods: A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four genetic variants of TNFSF4 gene promoter (rs1234314, rs844644, rs844648 and rs12039904) were selected as genetic markers. Results: A pooled analysis revealed the association of rs1234314 and rs12039904 polymorphisms with SSc (OR 1.15, 95% CI 1.02 to 1.31; OR 1.18, 95% CI 1.08 to 1.29, respectively). Significant association of the four tested variants with patients with limited cutaneous SSc (lcSSc) was revealed (rs1234314 OR 1.22, 95% CI 1.07 to 1.38; rs844644 OR 0.91, 95% CI 0.83 to 0.99; rs844648 OR 1.10, 95% CI 1.01 to 1.20 and rs12039904 OR 1.20, 95% CI 1.09 to 1.33). Association of rs1234314, rs844648 and rs12039904 minor alleles with patients positive for anti-centromere antibodies (ACA) remained significant (OR 1.23, 95% CI 1.10 to 1.37; OR 1.12, 95% CI 1.01 to 1.25; OR 1.22, 95% CI 1.07 to 1.38, respectively). Haplotype analysis confirmed a protective haplotype associated with SSc, lcSSc and ACA positive subgroups (OR 0.88, 95% CI 0.82 to 0.96; OR 0.88, 95% CI 0.80 to 0.96; OR 0.86, 95% CI 0.77 to 0.97, respectively) and revealed a new risk haplotype associated with the same groups of patients (OR 1.14, 95% CI 1.03 to 1.26; OR 1.20, 95% CI 1.08 to 1.35; OR 1.23, 95% CI 1.07 to 1.42, respectively). Conclusions: The data confirm the influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in subsets of patients positive for lcSSc and ACA.

Published
2011

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