Search results for "Regulatory"
showing 10 items of 740 documents
Decreased proportions of CD4 + IL17+/CD4 + CD25 + CD127- and CD4 + IL17+/CD4 + CD25 + CD127 - FoxP3+ T cells in children with autoimmune thyroid dise…
2016
Until now, altered balance of Th1 and Th2 immune cells has been postulated to play an important role in the pathogenesis of autoimmune thyroid diseases (AITD). However, recent studies on thyroid diseases have suggested a new role for Th17 cells that have been classified as a new lineage, distinct from Th1, Th2 and Treg cells. Despite wide interest, the role of Th17 cells in the pathogenesis of inflammatory and autoimmune diseases is still debated. The aim of the study was to estimate the proportions of Th17/Treg T cells in peripheral blood from patients with Graves' disease (GD; n = 29, mean age 15.4 ± 5.1 years), Hashimoto's thyroiditis (HT; n = 39, mean age 15.2 ± 4.1 years) and in health…
Peroxisome proliferator-activated receptor alpha deficiency impairs regulatory T cell functions: Possible application in the inhibition of melanoma t…
2016
International audience; Regulatory T (Treg) cells are important to induce and maintain immunological self-tolerance. Although the progress accomplished in understanding the functional mechanism of Treg cells, intracellular molecules that control the mechanisms of their suppressive capacity are still on investigation. The present study showed that peroxisome proliferator-activated receptor-alpha deficiency impaired the suppressive activity of Treg cells on CD4(+)CD25(-) and CD8(+) T cell proliferation. In Treg cells, PPARα gene deletion also induced a decrease of migratory abilities, and downregulated the expression of chemokine receptors (CCR-4, CCR-8 and CXCR-4) and p27(KIP1) mRNA. Treg ce…
Analysis of allergic immune responses in humanized mice.
2015
Nowadays, more than 25% of the population in industrial countries are affected by IgE-mediated (atopic) allergic diseases such as allergic rhinitis, asthma and atopic eczema. Due to intensive research on basis of in vitro studies with human immune cells and different murine in vivo models of allergy fundamental mechanisms of allergic immune responses have been elucidated during the last years. However, human studies are restricted and the immune system of mice differs from the human immune system in several aspects so that the transferability of experimental results from mice to men is limited. Humanized mice represent a new tool to analyze the interaction of human immune cells under physio…
miR-21 antagonism abrogates Th17 tumor promoting functions in multiple myeloma
2020
Multiple myeloma (MM) is tightly dependent on inflammatory bone marrow microenvironment. IL-17 producing CD4+ T cells (Th17) sustain MM cells growth and osteoclasts-dependent bone damage. In turn, Th17 differentiation relies on inflammatory stimuli. Here, we investigated the role of miR-21 in Th17-mediated MM tumor growth and bone disease. We found that early inhibition of miR-21 in naive T cells (miR-21i-T cells) impaired Th17 differentiation in vitro and abrogated Th17-mediated MM cell proliferation and osteoclasts activity. We validated these findings in NOD/SCID-g-NULL mice, intratibially injected with miR-21i-T cells and MM cells. A Pairwise RNAseq and proteome/phosphoproteome analysis…
A multidimensional network approach reveals microRNAs as determinants of the mesenchymal colorectal cancer subtype
2016
Colorectal cancer (CRC) is a heterogeneous disease posing a challenge for accurate classification and treatment of this malignancy. There is no common genetic molecular feature that would allow for the identification of patients at risk for developing recurrences and thus selecting patients who would benefit from more stringent therapies still poses a major clinical challenge. Recently, an international multicenter consortium (CRC Subtyping Consortium) was established aiming at the classification of CRC patients in biologically homogeneous CRC subtypes. Four consensus molecular subtypes (CMSs) were identified, of which the mesenchymal CMS4 presented with worse prognosis signifying the impor…
NUPR1, a new target in liver cancer: implication in controlling cell growth, migration, invasion and sorafenib resistance
2016
AbstractSorafenib, an oral multikinase inhibitor, is the only approved agent for the treatment of advanced hepatocellular carcinoma (HCC). However, its benefits are modest, and as its mechanisms of action remain elusive, a better understanding of its anticancer effects is needed. Based on our previous study results, we investigated here the implication of the nuclear protein 1 (NUPR1) in HCC and its role in sorafenib treatment. NUPR1 is a stress-inducible protein that is overexpressed in various malignancies, but its role in HCC is not yet fully understood. We found that NUPR1 expression was significantly higher in primary human HCC samples than in the normal liver. Knockdown of NUPR1 signi…
Meta-analysis identifies novel risk loci and yields systematic insights into the biology of male-pattern baldness
2017
Male-pattern baldness (MPB) is a common and highly heritable trait characterized by androgen-dependent, progressive hair loss from the scalp. Here, we carry out the largest GWAS meta-analysis of MPB to date, comprising 10,846 early-onset cases and 11,672 controls from eight independent cohorts. We identify 63 MPB-associated loci (P<5 × 10−8, METAL) of which 23 have not been reported previously. The 63 loci explain ∼39% of the phenotypic variance in MPB and highlight several plausible candidate genes (FGF5, IRF4, DKK2) and pathways (melatonin signalling, adipogenesis) that are likely to be implicated in the key-pathophysiological features of MPB and may represent promising targets for the de…
The role of myoglobin in epithelial cancers: Insights from transcriptomics
2019
The muscle-associated respiratory protein myoglobin (MB) is expressed in multiple types of cancer, including breast and prostate tumors. In Kaplan-Meier analyses of the two tumor types, MB positivity is associated with favorable prognoses. Despite its well-characterized function in myocytes, the role of MB in cancer remains unclear. To study the impact of endogenous MB expression, small interfering RNA MB-knockdown cells were engineered using breast, prostate and colon cancer cell lines (MDA-MB468, LNCaP, DLD-1), and their transcriptomes were investigated using RNA-Seq at different oxygen levels. In MB-positive cells, increased expression of glycolytic genes was observed, which was possibly…
General control non-derepressible 2 (GCN2) in T cells controls disease progression of autoimmune neuroinflammation.
2016
Relapsing-remitting multiple sclerosis (MS)(2) is characterized by phases of acute neuroinflammation followed by spontaneous remission. Termination of inflammation is accompanied by an influx of regulatory T cells (Tregs).(3) The molecular mechanisms responsible for directing Tregs into the inflamed CNS tissue, however, are incompletely understood. In an MS mouse model we show that the stress kinase general control non-derepressible 2 (GCN2),(4) expressed in T cells, contributes to the resolution of autoimmune neuroinflammation. Failure to recover from acute inflammation was associated with reduced frequencies of CNS-infiltrating Tregs. GCN2 deficient Tregs displayed impaired migration to a…
Cohesin-dependent regulation of gene expression during differentiation is lost in cohesin-mutated myeloid malignancies.
2019
Cohesin complex disruption alters gene expression, and cohesin mutations are common in myeloid neoplasia, suggesting a critical role in hematopoiesis. Here, we explore cohesin dynamics and regulation of hematopoietic stem cell homeostasis and differentiation. Cohesin binding increases at active regulatory elements only during erythroid differentiation. Prior binding of the repressive Ets transcription factor Etv6 predicts cohesin binding at these elements and Etv6 interacts with cohesin at chromatin. Depletion of cohesin severely impairs erythroid differentiation, particularly at Etv6-prebound loci, but augments self-renewal programs. Together with corroborative findings in acute myeloid le…