Search results for "orphan receptor"
showing 10 items of 26 documents
The protein tyrosine kinase Tec regulates a CD44highCD62L- Th17 subset.
2010
Abstract The generation of Th17 cells has to be tightly controlled during an immune response. In this study, we report an increase in a CD44highCD62L− Th17 subset in mice deficient for the protein tyrosine kinase Tec. CD44highCD62L− Tec−/− CD4+ T cells produced enhanced IL-17 upon activation, showed increased expression levels of IL-23R and RORγt, and IL-23–mediated expansion of Tec−/− CD4+ T cells led to an increased production of IL-17. Tec−/− mice immunized with heat-killed Streptococcus pneumoniae displayed increased IL-17 expression levels in the lung postinfection with S. pneumoniae, and this correlated with enhanced pneumococcal clearance and reduced lung inflammation compared with T…
The germ cell nuclear factor (GCNF)
2005
The germ cell nuclear factor (GCNF), which is also known as RTR (retinoid receptor-related testis-associated receptor) is a member of the nuclear receptor superfamily. As a natural ligand remains to be discovered, GCNF is referred to as an orphan receptor. Owing to GCNF's unique features and its distant relation to any other known nuclear receptor it has been classified as the only member of the subgroup six and designated NR6A1 by the Receptor Nomenclature Committee (Duarte et al., 2002: Nucleic Acids Res 30: 364-368). To date, GCNF has been cloned from distinct vertebrate species, including zebrafish, Xenopus laevis, mouse, rat, and human. Cloning and characterization of the gene, domain …
Functional characterization of two human olfactory receptors expressed in the baculovirus Sf9 insect cell system
2005
Olfactory receptors (ORs) are the largest member of the G-protein-coupled receptors which mediate early olfactory perception in discriminating among thousands of odorant molecules. Assigning odorous ligands to ORs is a prerequisite to gaining an understanding of the mechanisms of odorant recognition. The functional expression of ORs represents a critical step in addressing this issue. Due to limitations in heterologous expression, very few mammal ORs have been characterized, and so far only one is from human origin. Consequently, OR function still remains poorly understood, especially in humans, whose genome encodes a restricted chemosensory repertoire compared with most mammal species. In …
The nuclear receptor PPARγ selectively inhibits Th17 differentiation in a T cell–intrinsic fashion and suppresses CNS autoimmunity
2009
T helper cells secreting interleukin (IL)-17 (Th17 cells) play a crucial role in autoimmune diseases like multiple sclerosis (MS). Th17 differentiation, which is induced by a combination of transforming growth factor (TGF)-beta/IL-6 or IL-21, requires expression of the transcription factor retinoic acid receptor-related orphan receptor gamma t (ROR gamma t). We identify the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR gamma) as a key negative regulator of human and mouse Th17 differentiation. PPAR gamma activation in CD4(+) T cells selectively suppressed Th17 differentiation, but not differentiation into Th1, Th2, or regulatory T cells. Control of Th17 differentia…
Early impairment of epigenetic pattern in neurodegeneration: Additional mechanisms behind pyrethroid toxicity
2019
Abstract Permethrin is a synthetic pyrethroid extensively used as anti-woodworm agent and for indoor and outdoor pest control. The main route of human exposure is through fruit, vegetable and milk intake. Low dosage exposure to permethrin during neonatal brain development (from postnatal day 6 to postnatal day 21) leads to dopamine decrease in rat striatum nucleus, oxidative stress and behavioural changes linked to the development of Parkinson's like neurodegeneration later in life. The aim of this study was to evaluate the expression of genes involved in the dopaminergic pathway and epigenetic regulatory mechanisms in adolescent rats treated with permethrin during neonatal brain developmen…
Increased levels of Th17 cells are associated with non-neuronal acetylcholine in COPD patients.
2014
T-lymphocytes, including Th17-cells and T-cells expressing acetylcholine (ACh), are key components of systemic inflammation in chronic obstructive pulmonary disease (COPD). We investigated whether ACh promotes Th17 cells in COPD. ACh, IL-17A, IL-22, RORγt, FOXP3 expression and AChIL-17A, AChIL-22, AChRORγt coexpression was evaluated in peripheral blood mononuclear cells (PBMC) from COPD patients (n=16), healthy smokers (HS) (n=12) and healthy control subjects (HC) (n=13) (cultured for 48 h with PMA) by flow cytometry. Furthermore, we studied the effect of Tiotropium (Spiriva®) (100 nM) and Olodaterol (1nM) alone or in combination, and of hemicholinium-3 (50 μM) on AChIL-17A, AChIL-22, AChRO…
The murine nuclear orphan receptor GCNF is expressed in the XY body of primary spermatocytes
1998
AbstractWe have studied the expression of the nuclear orphan receptor GCNF (germ cell nuclear factor) on the mRNA and protein level in pubertal and adult mouse testes. We show by Northern and Western blot analyses and by in situ hybridization that GCNF is expressed in spermatocytes and round spermatids of adult mouse testis suggesting that GCNF may be a transcriptional regulator of spermatogenesis. Since the GCNF protein is accumulated in the XY body of late pachytene spermatocytes, it may be involved in transcriptional inactivation of sex chromosomes.
Biophysical Characterization of TRPV2 Ion Channel
2012
TRPV2 is a member of the superfamily of the Transient Receptor Potential (TRP) ion channels. These channels are assembled into homotetramers and allow cations across the membrane in response to physico-chemical stimuli such as heat, pressure, osmotic changes, etc. TRPV2 is an orphan receptor, since no specific endogenous ligand has been identified yet. To better understand the role of TRPV2 and to go further into its function, sequence analysis of orthologs for TRPV2 has been performed in order to define common and differential architectural regions. Preliminary biophysical characterization such as thermal stability, and secondary structure composition analysis has been carried out on the d…
Characterization and DNA-binding properties of GRF, a novel monomeric binding orphan receptor related to GCNF and betaFTZ-F1
1999
0014-2956 (Print) Comparative Study Journal Article Research Support, Non-U.S. Gov't; A PCR approach has been used to isolate, from Bombyx mori, a cDNA encoding a novel orphan receptor (GRF) that is most closely related to Bombyx betaFTZ-F1 and to the vertebrate germ cell nuclear factor. The major GRF mRNA is detected in most tissues as an 8-kb transcript whose amount follows the circulating ecdysteroid concentration with a delay. The expression pattern of GRF is similar to that of the Bombyx homologue of the Drosophila early-late gene DHR3, and precedes that of betaFTZ-F1 in all stages and tissues examined. The GRF protein is thus likely to be required in many tissues, but in a temporally …
THU0231 IL-17 polarization of mait cells derive from the activation of two different pathways
2017
Background Primary Sjogren Syndrome (pSS) is a chronic inflammatory disorder affecting exocrine glands. Both IL-23 and the downstream cytokines IL-17 and IL-22 are recognised as key players in the disease. Therefore, the identification of the cellular sources and inducers of IL-17 is crucial in the understanding of the drivers of inflammation in pSS. Mucosal-associated invariant T (MAIT) cells recognize riboflavin derivatives presented by the MHC class I-like molecule MR1. Objectives Recently, MAIT cells have been implicated in the pathogenesis of autoimmune disorders and found expanded in salivary glands of pSS patients. Their expression of IL7R and IL23R, makes them potential contributors…