A Proteomic Analysis Reveals That Snail Regulates the Expression of the Nuclear Orphan Receptor Nuclear Receptor Subfamily 2 Group F Member 6 (Nr2f6) and Interleukin 17 (IL-17) to Inhibit Adipocyte Differentiation

The regulation of human Th17 cell effector function by Treg cells (regulatory T-cells) is poorly understood. In the present study, we report that human Treg (CD4+CD25+) cells inhibit the proliferative response of Th17 cells but not their capacity to secrete IL (interleukin)-17. However, they could inhibit proliferation and cytokine production by Th1 and Th2 cells as determined by IFN-γ (interferon-γ) and IL-5 biosynthesis. Currently, as there is interest in the role of IL-17-producing cells and Treg cells in chronic inflammatory diseases in humans, we investigated the presence of CD4+CD25+ T-cells and IL-17 in inflammation in the human lung. Transcripts for IL-17 were expressed in mononuclear cells and purified T-cells from lung tissue of patients with chronic pulmonary inflammation and, when activated, these cells secrete soluble protein. The T-cell-specific transcription factors RORCv2 (retinoic acid-related orphan receptor Cv2; for Th17) and FOXP3 (forkhead box P3; for Treg cells) were enriched in the T-cell fraction of lung mononuclear cells. Retrospective stratification of the patient cohort into those with COPD (chronic obstructive pulmonary disease) and non-COPD lung disease revealed no difference in the expression of IL-17 and IL-23 receptor between the groups. We observed that CD4+CD25+ T-cells were present in comparable numbers in COPD and non-COPD lung tissue and with no correlation between the presence of CD4+CD25+ T-cells and IL-17-producing cells. These results suggest that IL-17-expressing cells are present in chronically inflamed lung tissue, but there is no evidence to support this is due to the recruitment or expansion of Treg cells.

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Deficiency of Th17 cells in hyper IgE syndrome due to mutations in STAT3

Journal of Experimental Medicine ◽

10.1084/jem.20080218 ◽

2008 ◽

Vol 205 (7) ◽

pp. 1551-1557 ◽

Cited By ~ 487

Author(s):

Cindy S. Ma ◽

Gary Y.J. Chew ◽

Nicholas Simpson ◽

Archana Priyadarshi ◽

Melanie Wong ◽

...

Keyword(s):

Th17 Cells ◽

Immunoglobulin E ◽

Orphan Receptor ◽

Primary Immune Deficiency ◽

Interleukin 17 ◽

Th 17 ◽

Infection Susceptibility ◽

Fungal Antigens

Hyper–immunoglobulin E syndrome (HIES) is a primary immune deficiency characterized by abnormal and devastating susceptibility to a narrow spectrum of infections, most commonly Staphylococcus aureus and Candida albicans. Recent investigations have identified mutations in STAT3 in the majority of HIES patients studied. Despite the identification of the genetic cause of HIES, the mechanisms underlying the pathological features of this disease remain to be elucidated. Here, we demonstrate a failure of CD4+ T cells harboring heterozygous STAT3 mutations to generate interleukin 17–secreting (i.e., T helper [Th]17) cells in vivo and in vitro due to a failure to express sufficient levels of the Th17-specific transcriptional regulator retinoid-related orphan receptor γt. Because Th17 cells are enriched for cells with specificities against fungal antigens, our results may explain the pattern of infection susceptibility characteristic of patients with HIES. Furthermore, they underscore the importance of Th17 responses in normal host defense against the common pathogens S. aureus and C. albicans.

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The Effect of Vitamin A Supplementation on Retinoic Acid-Related Orphan Receptor γt (RORγt) and Interleukin-17 (IL-17) Gene Expression in Avonex-Treated Multiple Sclerotic Patients

Journal of Molecular Neuroscience ◽

10.1007/s12031-013-0058-9 ◽

2013 ◽

Vol 51 (3) ◽

pp. 749-753 ◽

Cited By ~ 16

Author(s):

Niyaz Mohammadzadeh Honarvar ◽

Mohammad Hossein Harirchian ◽

Fariba Koohdani ◽

Feridoun Siassi ◽

Mina Abdolahi ◽

...

Keyword(s):

Gene Expression ◽

Retinoic Acid ◽

Vitamin A ◽

Orphan Receptor ◽

Interleukin 17 ◽

Vitamin A Supplementation

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Inactivation of the Nuclear Orphan Receptor COUP-TFII by Small Chemicals

ACS Chemical Biology ◽

10.1021/acschembio.6b00593 ◽

2017 ◽

Vol 12 (3) ◽

pp. 654-663 ◽

Cited By ~ 7

Author(s):

Rémy Le Guével ◽

Frédérik Oger ◽

Celia P. Martinez-Jimenez ◽

Maud Bizot ◽

Céline Gheeraert ◽

...

Keyword(s):

Orphan Receptor ◽

Nuclear Orphan Receptor

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The Orphan Nuclear Receptor 4A1: A Potential New Therapeutic Target for Metabolic Diseases

Journal of Diabetes Research ◽

10.1155/2018/9363461 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Lei Zhang ◽

Qun Wang ◽

Wen Liu ◽

Fangyan Liu ◽

Ailing Ji ◽

...

Keyword(s):

Skeletal Muscle ◽

Lipid Metabolism ◽

Nuclear Receptor ◽

Metabolic Diseases ◽

Early Response ◽

Orphan Receptor ◽

Special Focus ◽

Orphan Nuclear Receptor ◽

Physiological Functions ◽

The Impact

Orphan nuclear receptor 4A1 (NR4A1) is a transcriptional factor of the nuclear orphan receptor (NR4A) superfamily that has sparked interest across different research fields in recent years. Several studies have demonstrated that ligand-independent NR4A1 is an immediate-early response gene and the protein product is rapidly induced by a variety of stimuli. Hyperfunction or dysfunction of NR4A1 is implicated in various metabolic processes, including carbohydrate metabolism, lipid metabolism, and energy balance, in major metabolic tissues, such as liver, skeletal muscle, pancreatic tissues, and adipose tissues. No endogenous ligands for NR4A1 have been identified, but numerous compounds that bind and activate or inactivate nuclear NR4A1 or induce cytoplasmic localization of NR4A1 have been identified. This review summarizes recent advances in our understanding of the molecular biology and physiological functions of NR4A1. And we focus on the physiological functions of NR4A1 receptor to the development of the metabolic diseases, with a special focus on the impact on carbohydrate and lipid metabolism in skeletal muscle, liver, adipose tissue, and islet.

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