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1.
Sci Rep ; 12(1): 11821, 2022 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-35821240

RESUMEN

T cell exhaustion refers to a dysfunctional state in which effector T cells present a decreased ability to proliferate and to produce cytokines, while the co-expression of inhibitory receptors increases. We investigated global and donor-specific T cell responses in a cohort of stable, living-donor kidney transplant patients that received similar immunosuppression. After transplantation, an increase in the ratio of TIGIT + /CD226 + in mCD4 + T cells (r = 0.47, p = 0.01), and a decrease of CD226 + TIGIT-mCD4 + T cells was observed (r = - 0.55, p = 0.001). This leads to an increase of dysfunctional T cells in patients far from transplantation. In mCD8 + T cells, a decrease of IL-2 production after mitogenic stimulation was observed far from transplantation. Phenotypic analyses revealed an increase of mCD8 + T cells co-expressing PD-1 and TIGIT over time (r = 0.51, p = 0.02). After donor-specific stimulation, the ability of CD4 + T cells to proliferate was decreased compared with third parties. CD4 + T cells expressing CD226 and TIGIT were correlated with allospecific CD4 + proliferation (r = 0.68, p = 0.04). Our study suggests that after kidney transplantation a T cell hyporesponsiveness appears over time, driven by a dysregulation of CD226/TIGIT axis in mCD4 + T cells, associated with an increase of PD1 + TIGIT + in mCD8 + T cells.


Asunto(s)
Antígenos de Diferenciación de Linfocitos T , Linfocitos T CD4-Positivos , Trasplante de Riñón , Receptores Inmunológicos , Antígenos de Diferenciación de Linfocitos T/inmunología , Citocinas/inmunología , Humanos , Receptores Inmunológicos/inmunología , Inmunología del Trasplante
2.
Nucleic Acids Res ; 48(3): 1206-1224, 2020 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-31799607

RESUMEN

The histone demethylase LSD1 is a key chromatin regulator that is often deregulated in cancer. Its ortholog, dLsd1 plays a crucial role in Drosophila oogenesis; however, our knowledge of dLsd1 function is insufficient to explain its role in the ovary. Here, we have performed genome-wide analysis of dLsd1 binding in the ovary, and we document that dLsd1 is preferentially associated to the transcription start site of developmental genes. We uncovered an unanticipated interplay between dLsd1 and the GATA transcription factor Serpent and we report an unexpected role for Serpent in oogenesis. Besides, our transcriptomic data show that reducing dLsd1 levels results in ectopic transposable elements (TE) expression correlated with changes in H3K4me2 and H3K9me2 at TE loci. In addition, our results suggest that dLsd1 is required for Piwi dependent TE silencing. Hence, we propose that dLsd1 plays crucial roles in establishing specific gene expression programs and in repressing transposons during oogenesis.


Asunto(s)
Elementos Transponibles de ADN/genética , Proteínas de Drosophila/genética , Factores de Transcripción GATA/genética , Oogénesis/genética , Oxidorreductasas N-Desmetilantes/genética , Animales , Proteínas Argonautas/genética , Cromatina/genética , Drosophila melanogaster/genética , Drosophila melanogaster/crecimiento & desarrollo , Femenino , Regulación del Desarrollo de la Expresión Génica/genética , Genes del Desarrollo/genética , Histonas/genética , Ovario/crecimiento & desarrollo , Ovario/metabolismo , Sitio de Iniciación de la Transcripción
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