Biology subjects

Tison, A.

Publications and source records attributed to Tison, A..

4 recordsLinked to original sources

bioRxiv2024

B-Cell Involvement in Immune Checkpoint Inhibitor-Induced Lichen Planus: A Comparative Analysis with Non-Drug-Related Lichen Planus.

BackgroundImmune checkpoint inhibitors (ICI) have significantly improved cancer prognosis but can lead to immune-related adverse events (irAE), including cutaneous manifestations affecting 30% to 60% of ICI-treated patients. However, the physiopathology of cutaneaous irAE remains unclear. ObjectiveThis study investigated the immune infiltration in tissues affected by cutaneous irAE to elucidate their contribution to the pathogenesis of these toxicities. MethodsSkin biopsies from 6 patients with ICI-induced lichenoid eruptions were compared using imaging mass cytometry to samples from 7 controls with non-drug-related lichen planus. ResultsT cells were the predominant cell type within the inflammatory infiltrate in all samples, but we observed a reduced T-cell infiltration and an increased B-cell frequency in ICI-induced lichen planus compared to non-drug related lichen planus. Among B cells, we observed a significant decrease in IgD-CD27-double-negative B cells and an increase in IgD+CD27-naive B cells. Spatial analysis demonstrated that infiltrating B cells were organized in aggregates close to T cells in ICI-induced lichen planus. LimitationsThis is a retrospective single-center study with a relatively small sample size. ConclusionThis study sheds light on the involvement of B cells in the pathogenesis of ICI-induced lichen planus, suggesting distinct immunological mechanisms from non-drug-related lichen planus. CAPSULE SUMMARYO_LILichenoid manifestations are a common but understudied side effect occurring in patients receiving anti-PD-1 antibodies. C_LIO_LIICI-induced lichen planus displays distinct physiopathology from non-drug-related lichen planus, with a decrease of T-cell infiltration concomitantly to the increase of B cells organized in aggregates. C_LI

immunology↗

bioRxiv2023

MAFB drives differentiation by permitting WT1 binding to podocyte 1 specific promoters

Podocytes are highly specialized cells, but their chromatin status and the precise molecular events leading to their differentiation remain poorly defined. Here we used ChIP-Seq analysis for H3K4me3, H3K4me1 and H3K27me3 to establish the histone methylation map in adult mouse podocytes. Our data demonstrate open chromatin across podocyte specific genes and reveals that genes expressed in the mesoderm lineage become actively repressed upon podocyte differentiation. To better understand the transcriptional control of podocyte differentiation, we studied the role of transcription factor MAFB. ChIP-Seq experiments and functional analysis in conditional knockout mice identified a set of direct MAFB targets including Nphs1, Nphs2, Vegfa and Tcf21. Loss of MafB led to the deposition of extracellular matrix, progressive foot process effacement, and kidney disease. ChIP experiments in knockout animals revealed that during development MAFB is essential for H3K4me3 methylation and the recruitment of WT1 to the promoters of the podocyte specific genes Nphs1 and Nphs2. Taken together our data reveal the crucial function of MAFB by permitting chromatin accessibility at podocyte-specific genes during development and maintaining terminal differentiation in adults.

developmental biology↗

bioRxiv2022

Adrenal cortex size, homeostasis and tumorigenesis is regulated by gonadal hormones via androgen receptor/β-catenin signalling crosstalk.

Female bias is highly prevalent among adrenal cortex hyperplasia and neoplasia, but the reasons behind this phenomenon are poorly understood. In this article, we show that overexpression of the secreted WNT agonist R-spondin-1 leads to ectopic activation of WNT/{beta}-catenin signalling and causes sex-specific adrenocortical hyperplasia in mice. While female adrenals show ectopic proliferation, male adrenals display excessive immune system activation and cortical thinning. Using a combination of genetic manipulations and hormonal treatment, we show that gonadal androgens suppress ectopic proliferation in the adrenal cortex and determine the selective activation of WNT-related genes Axin2 and Wnt4. Notably, genetic removal of androgen receptor (AR) from adrenocortical cells restores the mitogenic effect of WNT/{beta}-catenin signalling. This is the first demonstration that AR activity in the adrenal cortex determines susceptibility to canonical WNT signalling-induced hyperplasia. TeaserActivation of R-spondin signaling in the adrenal cortex leads to a sexually dimorphic phenotype causing tumors in females and immune cell recruitment in males

cancer biology↗

bioRxiv2020

Direct activation of RA signaling in cardiomyocytes protects hearts from apoptosis after myocardial infarction in mice

Retinoic acid (RA) is an essential signaling molecule for cardiac development and plays a protective role in the heart after myocardial infarction (MI). In both cases, the effect of RA signaling on cardiomyocytes, the principle cell type of the heart, has been reported to be indirect. Here we have developed an inducible murine transgenic RA-reporter line using CreERT2 technology that permits lineage tracing of RA-responsive cells and faithfully recapitulates endogenous RA activity in multiple organs during embryonic development. Strikingly, we have observed a direct RA response in cardiomyocytes during mid-late gestation and after MI. Ablation of RA signaling through deletion of the Aldh1a1/a2/a3 genes encoding RA-synthesizing enzymes leads to increased cardiomyocyte apoptosis in adults subjected to MI. RNA sequencing analysis reveals Tgm2 and Ace1, two genes with well-established links to cardiac repair, as potential targets of RA signaling in primary cardiomyocytes, thereby providing novel links between the RA pathway and heart disease.

developmental biology↗