Examinando por Autor "Gisbert, Javier P."

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Human intestinal pro-inflammatory CD11chighCCR2+CX3CR1+ macrophages, but not their tolerogenic CD11c−CCR2−CX3CR1− counterparts, are expanded in inflammatory bowel disease
(Springer Nature, 2018) Bernardo, David; Marin, Alicia C; Fernández-Tomé, Samuel; Montalban-Arqués, Ana; Carrasco, A; Tristan, E; Ortega Moreno, Lorena; Mora-Gutierrez, Irene; Diaz-Guerra, A; Caminero-Fernández, R; Miranda, P; Casals, F; Caldas, M; Jiménez, M; Casabona, Sergio; de la Morena, F; Esteve, M; Santander, Cecilio; Chaparro, María; Gisbert, Javier P.
Although macrophages (Mϕ) maintain intestinal immune homoeostasis, there is not much available information about their subset composition, phenotype and function in the human setting. Human intestinal Mϕ (CD45+HLA-DR+CD14+CD64+) can be divided into subsets based on the expression of CD11c, CCR2 and CX3CR1. Monocyte-like cells can be identified as CD11chighCCR2+CX3CR1+ cells, a phenotype also shared by circulating CD14+ monocytes. On the contrary, their Mϕ-like tissue-resident counterparts display a CD11c−CCR2−CX3CR1− phenotype. CD11chigh monocyte-like cells produced IL-1β, both in resting conditions and after LPS stimulation, while CD11c− Mϕ-like cells produced IL-10. CD11chigh pro-inflammatory monocyte-like cells, but not the others, were increased in the inflamed colon from patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. Tolerogenic IL-10-producing CD11c− Mϕ-like cells were generated from monocytes following mucosal conditioning. Finally, the colonic mucosa recruited circulating CD14+ monocytes in a CCR2-dependent manner, being such capacity expanded in IBD. Mϕ subsets represent, therefore, transition stages from newly arrived pro-inflammatory monocyte-like cells (CD11chighCCR2+CX3CR1+) into tolerogenic tissue-resident (CD11c−CCR2−CX3CR1−) Mϕ-like cells as reflected by the mucosal capacity to recruit circulating monocytes and induce CD11c− Mϕ. The process is nevertheless dysregulated in IBD, where there is an increased migration and accumulation of pro-inflammatory CD11chigh monocyte-like cells.
Immunomodulatory E ect of Gut Microbiota-Derived Bioactive Peptides on Human Immune System from Healthy Controls and Patients with Inflammatory Bowel Disease
(MDPI, 2019) Fernández-Tomé, Samuel; Marin, Alicia C; Ortega Moreno, Lorena; Baldan-Martin, Montse; Mora-Gutierrez, Irene; Lanas-Gimeno, Aitor; Moreno-Monteagudo, Jose Andrés; Santander, Cecilio; Sánchez, Borja; Chaparro, María; Gisbert, Javier P.; Bernardo, David
Bioactive peptides secreted by probiotic Bifidobacterium longum (peptide B7) and opportunistic pathogen Bacteroides fragilis (peptide B12) modulate the intestinal cytokine milieu in health. Here, we characterized their capacity to modulate both the mucosal cytokine production and the phenotype of circulating antigen presenting cells (APCs) in active inflammatory bowel disease (IBD). The IBD mucosa produced higher levels of pro-inflammatory cytokines referred to healthy controls (HCs). Peptides B7 and B12, however, did not ameliorate the mucosal cytokine milieu in IBD. Human circulating APCs (B-cells, monocytes, plasmacytoid dendritic cells (pDCs), and conventional dendritic cells (cDCs)) were characterized by flow cytometry in presence/absence of the peptides. Circulating B-cells, monocytes, and cDCs from IBD patients were more activated than those from HCs. Peptide B7, but not B12, decreased CCR2 expression on all APC subsets from HC, but not IBD patients. Moreover, both peptides tend to further increase their pro-inflammatory profile in IBD. In summary, IBD patients display mucosal and circulating APC pro-inflammatory properties. Peptide B7 immunomodulatory capacity elicited over circulating APCs from HC, but not IBD patients, suggests the presence of disrupted modulatory mechanisms for this peptide in IBD. Future studies should address the effect of bacteria-derived immunomodulatory peptides in non-inflamed (quiescent) IBD patients.
Long Non-Coding RNA Signatures in the Ileum and Colon of Crohn’s Disease Patients and Effect of Anti-TNF-alpha Treatment on Their Modulation
(MDPI, 2023) Baldan-Martin, Montse; Rubín de Célix, Cristina; Orejudo, Macarena; Ortega Moreno, Lorena; Fernández-Tomé, Samuel; Soleto, Irene; Ramírez, Cristina; Arroyo, Ricardo; Fernández, Paloma; Santander, Cecilio; Moreno-Monteagudo, Jose Andrés; Casanova, María José; Casals, Fernando; Casabona, Sergio; Becerro, Irene; Lozano, Juan J; Aransay, Ana Maria; Chaparro, María; Gisbert, Javier P.
Biological therapies only benefit one-third of patients with Crohn’s disease (CD). For this reason, a deeper understanding of the mechanisms by which biologics elicit their effect on intestinal mucosa is needed. Increasing evidence points toward the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of CD, although their role remains poorly studied. We aimed to characterize lncRNA profiles in the ileum and colon from CD patients and evaluate the effect of anti-TNF-α treatment on their transcription. Terminal ileum and left colon samples from 30 patients (active CD = 10, quiescent CD = 10, and healthy controls (HCs) = 10) were collected for RNA-seq. The patients were classified according to endoscopic activity. Furthermore, biopsies were cultured with infliximab, and their transcriptome was determined by Illumina gene expression array. A total of 678 differentially expressed lncRNAs between the terminal ileum and left colon were identified in HCs, 438 in patients with quiescent CD, and 468 in patients with active CD. Additionally, we identified three new lncRNAs in the ileum associated with CD activity. No differences were observed when comparing the effect of infliximab according to intestinal location, presence of disease (CD vs. HC), and activity (active vs. quiescent). The expression profiles of lncRNAs are associated with the location of intestinal tissue, being very different in the ileum and colon. The presence of CD and disease activity are associated with the differential expression of lncRNAs. No modulatory effect of infliximab has been observed in the lncRNA transcriptome.
Long Non-Coding RNAs and Their Potential Role as Biomarkers in Inflammatory Bowel Disease
(MDPI, 2024-08-13) Ortega Moreno, Lorena; Chaparro, María; Gisbert, Javier P.
Inflammatory bowel disease is a chronic inflammatory disease that encompasses entities such as Crohn’s disease and ulcerative colitis. Its incidence has risen in newly industrialised countries over time, turning it into a global disease. Lately, studies on inflammatory bowel disease have focused on finding non-invasive and specific biomarkers. Long non-coding RNAs may play a role in the pathophysiology of inflammatory bowel disease and therefore they may be considered as potential biomarkers for this disease. In the present article, we review information in the literature on the relationship between long non-coding RNAs and inflammatory bowel disease. We especially focus on understanding the potential function of these RNAs as non-invasive biomarkers, providing information that may be helpful for future studies in the field.
Profiling of Human Circulating Dendritic Cells and Monocyte Subsets Discriminates Between Type and Mucosal Status in Patients With Inflammatory Bowel Disease
(2021) Ortega Moreno, Lorena; Fernández-Tomé, Samuel; Chaparro, María; Marin, Alicia C; Mora-Gutierrez, Irene; Santander, Cecilio; Baldan-Martin, Montse; Gisbert, Javier P.; Bernardo, David
[Background]: Intestinal dendritic cells (DC) and macrophages drive disease progression in patients with inflammatory bowel disease (IBD). We aimed to characterize the activation and homing profile of human circulating DC and monocyte subsets in healthy control patients (CP) and IBD patients.
Serum adipokines as non‑invasive biomarkers in Crohn’s disease
(2020) Ortega Moreno, Lorena; Sanz García, Ancor; Fernández de la Fuente, Marina J; Arroyo Solera, Ricardo; Fernández-Tomé, Samuel; Marin, Alicia C; Mora-Gutierrez, Irene; Fernández, Paloma; Baldan-Martin, Montse; Chaparro, María; Gisbert, Javier P.; Bernardo, David
Adipose tissue secretes molecules that can promote activity in Crohn’s disease. We aimed to evaluate the role of serum adipokines as possible biomarkers in Crohn’s disease. Serum samples were obtained from 40 patients with endoscopically active or quiescent Crohn’s disease and 36 healthy controls. Serum leptin, ghrelin, resistin and adiponectin levels were analysed by Multiplex in a Luminex 200 system technology. Receiver Operating Characteristic curves were performed to evaluate the adipokines discriminatory capacity. A logistic regression adjusted by possible confounders (i.e. gender, age, BMI) was performed for those adipokines that showed an area under the curve> 0.7. No diferences were found in age, gender or BMI among groups. Distribution for serum resistin was diferent among the three groups of study, and only this adipokine showed an area under the curve of 0.75 comparing actives patients and healthy control groups. Resistin median concentration was selected as a cut-of for a logistic regression analysis; odds ratio along its 95% confdence interval adjusted by gender, age, and BMI yielded a value of 5.46 (1.34–22.14) comparing actives patients and healthy controls. High concentration of serum resistin is probably associated to activity, being this association independent of gender, age or BMI.