Search results for "orphan receptor"
showing 10 items of 26 documents
Chemopreventive effect of oleuropein in colitis-associated colorectal cancer in c57bl/6 mice
2015
Scope The main phenolic secoiridoid oleuropein and active constituent from olive tree (Olea europaea, Oleaceae), has demonstrated anti-inflammatory properties in intestinal inflammation and anti-tumoral effects in different cancer cells. In this study, we evaluated the chemoprevention of oleuropein in a model of azoxymethane (AOM)/Dextran sulfate sodium (DSS)-induced colorectal cancer (CRC) in C57BL/6 mice and the modulatory effect on the Th17 response in DSS acute colitis. Methods and results Oleuropein protected from AOM/DSS-induced CRC by improving clinical symptoms, disease activity index score as well as suppressed the growth and multiplicity of colonic tumors. Treatment with oleuropei…
Targeting cellular fatty acid synthesis limits T helper and innate lymphoid cell function during intestinal inflammation and infection
2019
CD4+ T cells contribute critically to a protective immune response during intestinal infections, but have also been implicated in the aggravation of intestinal inflammatory pathology. Previous studies suggested that T helper type (Th)1 and Th17 cells depend on de novo fatty acid (FA) synthesis for their development and effector function. Here, we report that T-cell-specific targeting of the enzyme acetyl-CoA carboxylase 1 (ACC1), a major checkpoint controlling FA synthesis, impaired intestinal Th1 and Th17 responses by limiting CD4+ T-cell expansion and infiltration into the lamina propria in murine models of colitis and infection-associated intestinal inflammation. Importantly, pharmacolog…
IL-17 polarization of MAIT cells is derived from the activation of two different pathways
2017
MAIT cells are expanded in salivary glands of patients with Sjogren's syndrome and are IL-17 polarized. IL-7 and IL-23 induce IL-17 production activating two different pathways: IL-7 stimulation induces in fact a significant STAT3 and HIF1alpha upregulation, conversely, IL-23 stimulation significantly induces RORc overexpression in MAIT cells of patients with Sjogren's syndrome.
Interaction between ROR1 and MuSK activation complex in myogenic cells
2017
The ROR family of receptor tyrosine kinases, ROR1 and ROR2, is known to play an important role during skeletal muscle regeneration. ROR1 has a critical role in regulating satellite cell (SC) proliferation during muscle regeneration, and proinflammatory cytokines such as TNF-α and IL-1β can induce expression of ROR1 in myogenic cells via NF-κB activation. While searching for ROR1-interacting proteins in myogenic cells, we identified MuSK as a ROR1-binding protein. MuSK interacts with and phosphorylates ROR1 at the cytoplasmic proline-rich domain. ROR1 also interacts with the MuSK activator Dok-7 independently of MuSK interaction. Collectively, our results identified ROR1 as a new interacting…
A Weaning Reaction to Microbiota Is Required for Resistance to Immunopathologies in the Adult.
2019
International audience; Microbes colonize all body surfaces at birth and participate in the development of the immune system. In newborn mammals, the intestinal microbiota is first shaped by the dietary and immunological components of milk and then changes upon the introduction of solid food during weaning. Here, we explored the reactivity of the mouse intestinal immune system during the first weeks after birth and into adulthood. At weaning, the intestinal microbiota induced a vigorous immune response—a “weaning reaction”—that was programmed in time. Inhibition of the weaning reaction led to pathological imprinting and increased susceptibility to colitis, allergic inflammation, and cancer …
Tissue microenvironment dictates the fate and tumor-suppressive function of type 3 ILCs
2017
Nussbaum et al. found that tumor suppression through innate lymphoid cells (ILCs) cannot be predicted solely based on the ILC phenotype and lineage but that their immune properties are shaped both by their ontogeny and by the tissue microenvironment they reside in.
IRF4 regulates IL-17A promoter activity and controls RORγt-dependent Th17 colitis in vivo
2011
The transcription factor IRF4 is involved in several T-cell-dependent chronic inflammatory diseases. To elucidate the mechanisms for pathological cytokine production in colitis, we addressed the role of the IRF transcription factors in human inflammatory bowel disease (IBD) and experimental colitis.IRF levels and cytokine production in IBD patients were studied as well as the effects of IRF4 deficiency in experimental colitis.In contrast to IRF1, IRF5, and IRF8, IRF4 expression in IBD was augmented in the presence of active inflammation. Furthermore, IRF4 levels significantly correlated with IL-6 and IL-17 mRNA expression and to a lesser extent with IL-22 mRNA expression in IBD. To further …
Cloning of the human NCNF gene.
1998
We have cloned from a cDNA library of human testis tissue the human homologue to the mouse nuclear orphan receptor NCNF (neuronal cell nuclear factor). The open reading frame encodes a protein of 480 amino acids, the sequence of which (EMBL accession no. X99975) is 98.3% identical to the mouse homologue. Northern blot analysis of adult human tissues revealed a broad pattern of tissue expression. Similar to NCNF expression in mouse testis, two transcript forms of the single copy gene are expressed in human tissues. The two transcript forms which differ only in their 3'UTR, result in human from differential polyadenylation, in mouse from alternative splicing. Based on the high level of sequen…
Type 1 diabetic mellitus patients with increased atherosclerosis risk display decreased CDKN2A/2B/2BAS gene expression in leukocytes
2019
Background Type 1 diabetes mellitus (T1DM) patients display increased risk of cardiovascular disease (CVD) and are characterized by a diminished regulatory T (Treg) cell content or function. Previous studies have shown an association between decreased CDKN2A/2B/2BAS gene expression and enhanced CVD. In the present study the potential relationship between CDKN2A/2B/2BAS gene expression, immune cell dysfunction and increased cardiovascular risk in T1DM patients was explored. Methods A cross-sectional study was performed in 90 subjects divided into controls and T1DM patients. Circulating leukocyte subpopulations analysis by flow cytometry, expression studies on peripheral blood mononuclear cel…
T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma.
2007
T cell functional differentiation is mediated by lineage-specific transcription factors. T helper 17 (Th17) has been recently identified as a distinct Th lineage mediating tissue inflammation. Retinoic acid receptor-related orphan receptor gamma (ROR gamma) was shown to regulate Th17 differentiation; ROR gamma deficiency, however, did not completely abolish Th17 cytokine expression. Here, we report Th17 cells highly expressed another related nuclear receptor, ROR alpha, induced by transforming growth factor-beta and interleukin-6 (IL-6), which is dependent on signal transducer and activator of transcription 3. Overexpression of ROR alpha promoted Th17 differentiation, possibly through the c…