Search

Your search keyword '"Villanueva-Martín, Gonzalo"' showing total 15 results
Start Over Author "Villanueva-Martín, Gonzalo"
15 results on '"Villanueva-Martín, Gonzalo"'

4. Single-cell transcriptomic profiling reveals a pathogenic role of cytotoxic CD4+ T cells in giant cell arteritis

Author

Instituto de Salud Carlos III, Carmona, Elio G., Callejas-Rubio, José Luis, Raya, Enrique, Ríos-Fernández, Raquel, Villanueva-Martín, Gonzalo, Cid, María C., Hernández-Rodríguez, José, Ballestar, Esteban, Timmermann, Bernd, Ortego-Centeno, Norberto, Martin, Javier, Márquez, Ana, Instituto de Salud Carlos III, Carmona, Elio G., Callejas-Rubio, José Luis, Raya, Enrique, Ríos-Fernández, Raquel, Villanueva-Martín, Gonzalo, Cid, María C., Hernández-Rodríguez, José, Ballestar, Esteban, Timmermann, Bernd, Ortego-Centeno, Norberto, Martin, Javier, and Márquez, Ana

Abstract

Giant cell arteritis (GCA) is a systemic vasculitis mediated by an aberrant immunological response against the blood vessel wall. Although the pathogenic mechanisms that drive GCA have not yet been elucidated, there is strong evidence that CD4+ T cells are key drivers of the inflammatory process occurring in this vasculitis. The aim of this study was to further delineate the role of CD4+ T cells in GCA by applying single-cell RNA sequencing and T cell receptor (TCR) repertoire profiling to 114.799 circulating CD4+ T cells from eight GCA patients in two different clinical states, active and in remission, and eight healthy controls. Our results revealed an expansion of cytotoxic CD4+ T lymphocytes (CTLs) in active GCA patients, which expressed higher levels of cytotoxic and chemotactic genes when compared to patients in remission and controls. Accordingly, differentially expressed genes in CTLs of active patients were enriched in pathways related to granzyme-mediated apoptosis, inflammation, and the recruitment of different immune cells, suggesting a role of this cell type in the inflammatory and vascular remodelling processes occurring in GCA. CTLs also exhibited a higher clonal expansion in active patients with respect to those in remission. Drug repurposing analysis prioritized maraviroc, which targeted CTLs, as potentially repositionable for this vasculitis. In addition, effector regulatory T cells (Tregs) were decreased in GCA and showed lower expression of genes involved in their suppressive activity. These findings provide further insights into the pathogenic role of CD4+ T cells in GCA and suggest targeting CTLs as a potential therapeutic option.

Published
2024

5. Contribution of Telomere Length to Systemic Sclerosis Onset: A Mendelian Randomization Study

Author

Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Ministerio de Universidades (España), Rodríguez-Martín, Inmaculada, Villanueva-Martín, Gonzalo, Guillén del Castillo, Alfredo, Ortego-Centeno, N., Callejas-Rubio, J. L., Simeón, Carmen P., Martín, Javier, Acosta-Herrera, Marialbert, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Ministerio de Universidades (España), Rodríguez-Martín, Inmaculada, Villanueva-Martín, Gonzalo, Guillén del Castillo, Alfredo, Ortego-Centeno, N., Callejas-Rubio, J. L., Simeón, Carmen P., Martín, Javier, and Acosta-Herrera, Marialbert

Abstract

Although previous studies have suggested a relationship between telomere shortening and systemic sclerosis (SSc), the association between these two traits remains poorly understood. The objective of this study was to assess the causal relationship between telomere length in leukocytes (LTL) and SSc using the two-sample Mendelian randomization approach, with the genome-wide association study data for both LTL and SSc. The results of inverse-variance weighted regression (OR = 0.716 [95% CI 0.528–0.970], p = 0.031) and the Mendelian randomization pleiotropy residual sum and outlier method (OR = 0.716 [95% CI 0.563–0.911], p = 0.035) indicate an association between telomere length and SSc. Specifically, longer genetically predicted LTL is associated with a reduced risk of SSc. Sensitivity tests highlight the significant roles of the variants rs10936599 and rs2736100 annotated to the TERC and TERT genes, respectively. Our findings suggest an influence of telomere length in leukocytes on the development of SSc.

Published
2023

6. Non-classical circulating monocytes expressing high levels of microsomal prostaglandin E2 synthase-1 tag an aberrant IFN-response in systemic sclerosis

Author

Junta de Andalucía, Ministerio de Ciencia e Innovación (España), European Commission, Instituto de Salud Carlos III, Villanueva-Martín, Gonzalo, Acosta-Herrera, Marialbert, Carmona, Elio G., Kerick, Martin, Ortego-Centeno, Norberto, Callejas-Rubio, José Luis, Mages, Norbert, Börno, Stefan, Timmermann, Bernd, Bossini-Castillo, L., Martin, Javier, Klages, Sven, Junta de Andalucía, Ministerio de Ciencia e Innovación (España), European Commission, Instituto de Salud Carlos III, Villanueva-Martín, Gonzalo, Acosta-Herrera, Marialbert, Carmona, Elio G., Kerick, Martin, Ortego-Centeno, Norberto, Callejas-Rubio, José Luis, Mages, Norbert, Börno, Stefan, Timmermann, Bernd, Bossini-Castillo, L., Martin, Javier, and Klages, Sven

Abstract

Systemic sclerosis (SSc) is a complex disease that affects the connective tissue, causing fibrosis. SSc patients show altered immune cell composition and activation in the peripheral blood (PB). PB monocytes (Mos) are recruited into tissues where they differentiate into macrophages, which are directly involved in fibrosis. To understand the role of CD14+ PB Mos in SSc, a single-cell transcriptome analysis (scRNA-seq) was conducted on 8 SSc patients and 8 controls. Using unsupervised clustering methods, CD14+ cells were assigned to 11 clusters, which added granularity to the known monocyte subsets: classical (cMos), intermediate (iMos) and non-classical Mos (ncMos) or type 2 dendritic cells. NcMos were significantly overrepresented in SSc patients and showed an active IFN-signature and increased expression levels of PTGES, in addition to monocyte motility and adhesion markers. We identified a SSc-related cluster of IRF7+ STAT1+ iMos with an aberrant IFN-response. Finally, a depletion of M2 polarised cMos in SSc was observed. Our results highlighted the potential of PB Mos as biomarkers for SSc and provided new possibilities for putative drug targets for modulating the innate immune response in SSc.

Published
2023

7. Identification of Mechanisms by Which Genetic Susceptibility Loci Influence Systemic Sclerosis Risk Using Functional Genomics in Primary T Cells and Monocytes

Author

González-Serna, David, Shi, Chenfu, Kerick, Martin, Hankinson, James, Ding, James, McGovern, Amanda, Tutino, Mauro, Villanueva-Martín, Gonzalo, Ortego-Centeno, Norberto, Callejas, Jose Luis, Martin, Javier, Orozco, Gisela, González-Serna, David, Shi, Chenfu, Kerick, Martin, Hankinson, James, Ding, James, McGovern, Amanda, Tutino, Mauro, Villanueva-Martín, Gonzalo, Ortego-Centeno, Norberto, Callejas, Jose Luis, Martin, Javier, and Orozco, Gisela

Published
2023

9. Estudio de la influencia de la longitud de los telómeros como factor de riesgo en la esclerosis sistémica.

Author

Rodríguez-Martín, Inmaculada, Villanueva-Martín, Gonzalo, SIMON MATEO, CARMEN, Guillén, A., Ortego-Centeno, Norberto, Callejas, Jose Luis, Acosta-Herrera, Marialbert, Martin, Javier, Rodríguez-Martín, Inmaculada, Villanueva-Martín, Gonzalo, SIMON MATEO, CARMEN, Guillén, A., Ortego-Centeno, Norberto, Callejas, Jose Luis, Acosta-Herrera, Marialbert, and Martin, Javier

Published
2023

10. A single cell transcriptomic analysis reveals a pro-inflammatory profile in peripheral blood CD14+ monocytes of systemic sclerosis patients

Author

Villanueva-Martín, Gonzalo, Acosta-Herrera, Marialbert, Carmona, Elio G., Kerick, Martin, Ortego-Centeno, Norberto, Callejas-Rubio, José Luis, Mages, Norbert, Börno, Stefan, Klages, Sven, Timmermann, Bernd, Bossini-Castillo, Lara, Martin, Javier, Villanueva-Martín, Gonzalo, Acosta-Herrera, Marialbert, Carmona, Elio G., Kerick, Martin, Ortego-Centeno, Norberto, Callejas-Rubio, José Luis, Mages, Norbert, Börno, Stefan, Klages, Sven, Timmermann, Bernd, Bossini-Castillo, Lara, and Martin, Javier

Published
2023

11. The effect of body fat distribution on systemic sclerosis.

Author

Ministerio de Ciencia e Innovación (España), European Commission, Instituto de Salud Carlos III, European Science Foundation, Villanueva-Martín, Gonzalo, Acosta-Herrera, Marialbert, Kerick, Martin, López-Isac, Elena, Simeón, Carmen P., Calleja, José Luis, Assassi, Shervin, Beretta, Lorenzo, Allanore, Yannick, Proudman, Susanna, Nikpour, Mandana, Fonseca, Carmen, Denton, Christopher, Radstake, Timothy R. D. J., Mayes, Maureen D., Jiang, Xia, Martin, Javier, Bossini-Castillo, Lara, Ministerio de Ciencia e Innovación (España), European Commission, Instituto de Salud Carlos III, European Science Foundation, Villanueva-Martín, Gonzalo, Acosta-Herrera, Marialbert, Kerick, Martin, López-Isac, Elena, Simeón, Carmen P., Calleja, José Luis, Assassi, Shervin, Beretta, Lorenzo, Allanore, Yannick, Proudman, Susanna, Nikpour, Mandana, Fonseca, Carmen, Denton, Christopher, Radstake, Timothy R. D. J., Mayes, Maureen D., Jiang, Xia, Martin, Javier, and Bossini-Castillo, Lara

Abstract

Obesity contributes to a chronic proinflammatory state, which is a known risk factor to develop immune-mediated diseases. However, its role in systemic sclerosis (SSc) remains to be elucidated. Therefore, we conducted a two-sample mendelian randomization (2SMR) study to analyze the effect of three body fat distribution parameters in SSc. As instrumental variables, we used the allele effects described for single nucleotide polymorphisms (SNPs) in different genome-wide association studies (GWAS) for SSc, body mass index (BMI), waist-to-hip ratio (WHR) and WHR adjusted for BMI (WHRadjBMI). We performed local (pHESS) and genome-wide (LDSC) genetic correlation analyses between each of the traits and SSc and we applied several Mendelian randomization (MR) methods (i.e., random effects inverse-variance weight, MR-Egger regression, MR pleiotropy residual sum and outlier method and a multivariable model). Our results show no genetic correlation or causal relationship between any of these traits and SSc. Nevertheless, we observed a negative causal association between WHRadjBMI and SSc, which might be due to the effect of gastrointestinal complications suffered by the majority of SSc patients. In conclusion, reverse causality might be an especially difficult confounding factor to define the effect of obesity in the onset of SSc.

Published
2022

12. The effect of body fat distribution on systemic sclerosis.

Author

Villanueva-Martín, Gonzalo, Acosta-Herrera, Marialbert, Kerick, Martin, López-Isac, Elena, Simeón, Carmen P., Callejas, Jose Luis, Assassi, S., Beretta, Lorenzo, Allanore, Yannick, Proudman, Susan, Nikpour, M, Fonseca, Carmen, Denton, Christopher, Radstake, Timothy R. D. J., Mayes, Maureen D., Jiang, Xia, Martin, Javier, Bossini-Castillo, Lara, Villanueva-Martín, Gonzalo, Acosta-Herrera, Marialbert, Kerick, Martin, López-Isac, Elena, Simeón, Carmen P., Callejas, Jose Luis, Assassi, S., Beretta, Lorenzo, Allanore, Yannick, Proudman, Susan, Nikpour, M, Fonseca, Carmen, Denton, Christopher, Radstake, Timothy R. D. J., Mayes, Maureen D., Jiang, Xia, Martin, Javier, and Bossini-Castillo, Lara

Published
2022

13. Single cell transcriptome analysis reinforces the pro-inflammatory role of CD14+ monocytes in scleroderma patients.

Author

Villanueva-Martín, Gonzalo, Acosta-Herrera, Marialbert, Carmona, Elio G., Kerick, Martin, Ortego-Centeno, Norberto, Callejas-Rubio, José Luis, Mages, Norbert, Börno, Stefan, Klages, Sven, Timmermann, Bernd, Bossini-Castillo, Lara, Martin, Javier, Villanueva-Martín, Gonzalo, Acosta-Herrera, Marialbert, Carmona, Elio G., Kerick, Martin, Ortego-Centeno, Norberto, Callejas-Rubio, José Luis, Mages, Norbert, Börno, Stefan, Klages, Sven, Timmermann, Bernd, Bossini-Castillo, Lara, and Martin, Javier

Published
2022

14. Approaching Shared Pathophysiology in Immune-Mediated Diseases through Functional Genomics

Author

Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), González-Serna, David, Villanueva-Martín, Gonzalo, Acosta-Herrera, Marialbert, Márquez, Ana, Martín, Francisco, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), González-Serna, David, Villanueva-Martín, Gonzalo, Acosta-Herrera, Marialbert, Márquez, Ana, and Martín, Francisco

Abstract

Immune-mediated diseases (IMDs) are complex pathologies that are strongly influenced by environmental and genetic factors. Associations between genetic loci and susceptibility to these diseases have been widely studied, and hundreds of risk variants have emerged during the last two decades, with researchers observing a shared genetic pattern among them. Nevertheless, the pathological mechanism behind these associations remains a challenge that has just started to be understood thanks to functional genomic approaches. Transcriptomics, regulatory elements, chromatin interactome, as well as the experimental characterization of genomic findings, constitute key elements in the emerging understandings of how genetics affects the etiopathogenesis of IMDs. In this review, we will focus on the latest advances in the field of functional genomics, centering our attention on systemic rheumatic IMDs.

Published
2020

15. Puntuación de riesgo poligénico para la predicción del desarrollo de cardiomiopatía chagásica crónica.

Author

Alejandra Jaimes, Mayra, Borrego-Yaniz, Gonzalo, Villanueva-Martín, Gonzalo, Isabel González, Clara, Martín, Javier, and Acosta-Herrera, Marialbert

Abstract

Copyright of Biomédica: Revista del Instituto Nacional de Salud is the property of Instituto Nacional de Salud of Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2022

Catalog

Books, media, physical & digital resources
See catalog results