scholarly journals Liver X Receptor regulates Th17 and RORγt+ Treg cells by distinct mechanisms

2019 ◽  
Author(s):  
Sara M. Parigi ◽  
Srustidhar Das ◽  
Annika Frede ◽  
Rebeca F. Cardoso ◽  
Kumar Parijat Tripathi ◽  
...  
Keyword(s):  
Lymph Node ◽  
Nuclear Receptors ◽  
Th17 Cells ◽  
Immune Modulation ◽  
Treg Cells ◽  
Liver X Receptor ◽  
Commensal Bacteria ◽  
T Helper ◽  
Mesenteric Lymph ◽  
Th Cell

AbstractThe gastrointestinal microenvironment, dominated by dietary compounds and the commensal bacteria, is a major driver of intestinal CD4+ T helper (Th) cell differentiation. Dietary compounds can be sensed by nuclear receptors (NRs) that consequently exerts pleiotropic effects including immune modulation. However, how NRs regulate distinct intestinal Th subsets remain poorly understood. Here, we found that under homeostatic condition Liver X receptor (LXR), a sensor of cholesterol metabolites, controls RORγt+ Treg and Th17 cells in the intestine draining mesenteric lymph node (MLN). Mechanistically, while lack of LXR signaling in CD11c+ myeloid cells led to an increase in RORγt+ Treg, modulation of MLN Th17 was independent of LXR signaling in either immune or epithelial cells. Of note, LXRα modulated only the Th17 cells, but not RORγt+ Treg in the MLN and horizontal transfer of microbiota between LXRα−/− and WT mice was sufficient to partially increase the MLN Th17 in WT mice. While LXRα deficiency increased the abundance of Ruminococcaceae and Lachnospiraceae bacterial families compared to the WT littermates, microbiota ablation including ablation of SFB was not sufficient to dampen LXRα-mediated expansion of MLN Th17. Altogether, our results suggest that LXR modulates RORγt+ Treg and Th17 cells in the MLN through distinct mechanisms.

scholarly journals The protective effect of curcumin on rats with DSS-induced ulcerative colitis and its mechanisms

2021 ◽  
Author(s):  
Jing Guo ◽  
Yan-yan Zhang ◽  
Mei Sun ◽  
Ling-fen Xu
Keyword(s):  
Ulcerative Colitis ◽  
Th17 Cells ◽  
Dextran Sulfate ◽  
Activity Index ◽  
Disease Activity Index ◽  
Treg Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
T Helper ◽  
T Helper 17 ◽  
Inflammatory Bowel

Abstract Aim This study aimed to explore effect of curcumin on inflammatory bowel disease (IBD) in rats and its mechanism.Methods: A dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) rat model was established. The disease activity index (DAI) scores were calculated. The histopathological damage scores were determined by haematoxylin-eosin (H&E) staining. Regulatory T (Treg) cells and T helper 17 (Th17) cells in the spleen were analysed by flow cytometry. The levels of interleukin (IL)-10 and IL-17A were determined by enzyme-linked immunosorbent assay (ELISA). Results: Compared with the DSS model group, the curcumin group exhibited significantly reduced DAI scores and improvements in histopathological damage. The expression of CD4+IL-17+ Th17 cells was significantly lower and the expression of CD4+CD25+Foxp3+ Treg cells was significantly higher in the curcumin group than in the DSS group.Conclusion: Curcumin may be a new and effective treatment for IBD by regulating the balance of Treg/Th17 cells and the expression of IL-10 and IL-17A.

scholarly journals Myelin-specific T helper 17 cells promote adult hippocampal neurogenesis through indirect mechanisms

F1000Research ◽  
2017 ◽  
Vol 3 ◽  
pp. 169 ◽  
Author(s):  
Johannes Niebling ◽  
Annette E. Rünker ◽  
Sonja Schallenberg ◽  
Karsten Kretschmer ◽  
Gerd Kempermann
Keyword(s):  
T Cell ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Precursor Cells ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Lymphoid Tissues ◽  
Base Line ◽  
T Helper ◽  
Th Cell

CD4+ T cells provide a neuro-immunological link in the regulation of adult hippocampal neurogenesis, but the exact mechanisms underlying enhanced neural precursor cell proliferation and the relative contribution of different T helper (Th) cell subsets have remained unclear. Here, we explored the pro-proliferative potential of interleukin 17-producing T helper (Th17) cells, a developmentally and functionally distinct Th cell subset that is a key mediator of autoimmune neurodegeneration. We found that base-line proliferation of hippocampal precursor cells in a T cell-deficient mouse model of impaired hippocampal neurogenesis can be restored upon adoptive transfer with homogeneous Th17 populations enriched for myelin-reactive T cell receptors (TCR). In these experiments, enhanced proliferation was independent of direct interactions of infiltrating Th17 cells with precursor cells or neighboring cells in the hippocampal neurogenic niche. Complementary studies in immunocompetent mice identified several receptors for Th17 cell-derived cytokines with mRNA expression in hippocampal precursor cells and dentate gyrus tissue, suggesting that Th17 cell activity in peripheral lymphoid tissues might promote hippocampal neurogenesis through secreted cytokines.

scholarly journals Differential Levels of Regulatory T Cells and T-Helper-17 Cells in Women With Early and Advanced Endometriosis

2019 ◽  
Vol 104 (10) ◽  
pp. 4715-4729 ◽  
Author(s):  
Khaleque N Khan ◽  
Kazuo Yamamoto ◽  
Akira Fujishita ◽  
Hideki Muto ◽  
Akemi Koshiba ◽  
...  
Keyword(s):  
T Cell ◽  
Th17 Cells ◽  
Treg Cells ◽  
Lower Percentage ◽  
T Helper ◽  
T Helper 17 ◽  
Control Subjects ◽  
Cell Subpopulations ◽  
American Society ◽  
T Cell Subpopulations

Abstract Context Regulatory T (Treg) cells and T-helper-17 (Th17) cells may be involved in endometriosis. Information on the pattern of change in the percentages of Treg and Th17 cells in the peripheral blood (PB) and peritoneal fluid (PF) of women with early and advanced endometriosis is unclear. Objective To investigate the pattern of change in the percentages of Treg and Th17 cells in the PB and PF of women with early and advanced endometriosis. Methods We recruited 31 women with laparoscopically and histologically confirmed, revised American Society of Reproductive Medicine stage I-II endometriosis, 39 women with stage III-IV endometriosis, and 36 control subjects without visible endometriosis. PB and PF samples were collected and T-cell subpopulations analyzed by flow cytometry using specific monoclonal antibodies recognizing CD4+, CD25+, FOXP3+, and IL-17A+ markers. PF concentrations of TGF-β and IL-17 were measured by ELISA. Results The percentages of CD25+FOXP3+ Treg cells within the CD4+ T-cell population were significantly higher in the PF of women with advanced endometriosis than in either early endometriosis or in control subjects (P < 0.05 for both). A persistently lower percentage of CD4+IL-17A+ Th17 cells was found in both PB and PF of women with early and advanced endometriosis. Compared with IL-17 levels, PF levels of TGF-β were significantly higher in women with endometriosis (P = 0.01). Conclusion Our findings reconfirmed the current speculation that endometriosis is related to alteration of Treg and Th17 cells in the pelvis causing survival and implantation of ectopic endometrial lesions.

scholarly journals Balance between Regulatory T and Th17 Cells in Systemic Lupus Erythematosus: The Old and the New

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Alessia Alunno ◽  
Elena Bartoloni ◽  
Onelia Bistoni ◽  
Giuseppe Nocentini ◽  
Simona Ronchetti ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Lymphocytes ◽  
Lupus Erythematosus ◽  
Th17 Cells ◽  
Current Knowledge ◽  
Treg Cells ◽  
T Helper ◽  
Systemic Lupus ◽  
Target Organs

Pathogenic mechanisms underlying the development of systemic lupus erythematosus (SLE) are very complex and not yet entirely clarified. However, the pivotal role of T lymphocytes in the induction and perpetuation of aberrant immune response is well established. Among T cells, IL-17 producing T helper (Th17) cells and regulatory T (Treg) cells represent an intriguing issue to be addressed in SLE pathogenesis, since an imbalance between the two subsets has been observed in the course of the disease. Treg cells appear to be impaired and therefore unable to counteract autoreactive T lymphocytes. Conversely, Th17 cells accumulate in target organs contributing to local IL-17 production and eventually tissue damage. In this setting, targeting Treg/Th17 balance for therapeutic purposes may represent an intriguing and useful tool for SLE treatment in the next future. In this paper, the current knowledge about Treg and Th17 cells interplay in SLE will be discussed.

The Ratio of Treg/Th17 Cells Correlates with the Platelet Number in Different Disease State of Primary Immune Thrombocytopenia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4649-4649
Author(s):  
Lili Ji ◽  
Feng Li ◽  
Yanxia Zhan ◽  
Fanli Hua ◽  
Shanhua Zou ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Th17 Cells ◽  
Immune Thrombocytopenia ◽  
Conflicts Of Interest ◽  
Disease Onset ◽  
Treg Cells ◽  
Healthy Controls ◽  
T Helper ◽  
Platelet Number ◽  
Primary Immune Thrombocytopenia

Abstract Abstract 4649 Background: Primary immune thrombocytopenia (ITP) is an autoimmune heterogeneous disorder that is characterized by decreased platelet count. Regulatory T (Treg) cells and T helper type 17 (Th17) cells are two subtypes of CD4+T helper (Th) cells. They play opposite roles in immune tolerance and autoimmune diseases, while they share a common differentiation pathway. The imbalance of Treg/Th17 has been demonstrated in several autoimmune diseases. In this study, we aimed to investigate the ratio of the number of Tregs to the number of Th17 cells in ITP patients and evaluate the clinical implications of the alterations in this ratio. Methods: Thirty adult patients with newly diagnosed ITP enrolled in this study. Patients who needed treatment had been clinically followed up for 12 months. The percentages of CD4+CD25hiFoxp3+ Treg cells and CD3+CD4+IL-17-producing Th17 cells in these patients and healthy controls (n=17) were longitudinally analyzed by flow cytometry. Results: The percentage of Treg cells in ITP patients was significantly lower than that of healthy controls and the percentage of Th17 cells increased significantly at disease onset. It is suggested that the ratio of Treg/Th17 correlated with the disease activity. Conclusion: The ratio of Treg/Th17 might be relevant to the clinical diversity of ITP patients, and this Treg/Th17 ratio might have prognostic role in ITP patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals T Helper 17 Cells in Autoimmune Liver Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Masanori Abe ◽  
Yoichi Hiasa ◽  
Morikazu Onji
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Autoimmune Diseases ◽  
Th17 Cells ◽  
Transforming Growth Factor ◽  
Treg Cells ◽  
Reciprocal Relationship ◽  
Th2 Cells ◽  
T Helper ◽  
T Helper 17

Many autoimmune diseases are driven by self-reactive T helper (Th) cells. A new population of effector CD4+T cells characterized by the secretion of interleukin (IL)-17, referred to as Th17 cells, has been demonstrated to be phenotypically, functionally, and developmentally distinct from Th1 and Th2 cells. Because the liver is known to be an important source of transforming growth factor-βand IL-6, which are cytokines that are crucial for Th17 differentiation, it is very likely that Th17 cells contribute to liver inflammation and autoimmunity. In contrast, another distinct subset of T cells, regulatory T cells (Treg), downregulate immune responses and play an important role in maintaining self-tolerance. In addition, there is a reciprocal relationship between Th17 cells and Tregs, in development and effector functions, and the balance between Th17 and Treg cells can affect the outcome of immune responses, particularly in autoimmune diseases. In this review, we will focus on the latest investigative findings related to Th17 cells in autoimmune liver disease.

scholarly journals Melatonin, an Endogenous Hormone, Modulates Th17 Cells via the Reactive Oxygen Species/TXNIP/HIF-1α Axis to Alleviate Autoimmune Uveitis

2022 ◽  
Author(s):  
Dan Liang ◽  
Jun Huang ◽  
Zhuang Li ◽  
Yunwei Hu ◽  
Zuoyi Li ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Flow Cytometry ◽  
T Cells ◽  
Th17 Cells ◽  
Reactive Oxygen ◽  
Treg Cells ◽  
Oxygen Species ◽  
T Helper ◽  
Autoimmune Uveitis

Abstract Background Melatonin, an indoleamine produced by the pineal gland, plays a pivotal role in maintaining circadian rhythm homeostasis. Recently, the strong antioxidant and anti-inflammatory properties of melatonin have attracted attention of researchers. We evaluated the therapeutic efficacy of melatonin in experimental autoimmune uveitis (EAU), which is a representative animal model of human autoimmune uveitis. Methods EAU was induced in mice via immunization with the peptide interphotoreceptor retinoid binding protein 1-20 (IRBP1−20). melatonin was then administered via intraperitoneal injection to induce protection against EAU. With EAU induction for 14 days, clinical and histopathological scores were employed to evaluate the disease progression. T lymphocytes accumulation, the expression of inflammatory cytokines in the retinas were assessed via flow cytometry and RT-PCR. In vivo and in vitro experiments, T helper 1 (Th1), T helper 17 (Th17) and regulatory T (Treg) cells were detected via flow cytometry, the level reactive oxygen species(ROS) from CD4+ cells were tested via flow cytometry, and the expression of thioredoxin-interacting protein (TXNIP) and hypoxia-inducible factor 1 alpha (HIF-1α)proteins were also quantified via western blot analysis, to elucidate the mechanism of melatonin inhibiting EAU. Results Melatonin treatment resulted in notable attenuation of ocular inflammation in EAU mice, evidenced by decreasing optic disc edema, few signs of retinal vasculitis, and minimal retinal and choroidal infiltrates. Mechanistic studies revealed that melatonin restricted the proliferation of peripheral Th1 and Th17 cells and potentiated Treg cells by suppressing their transcription factors. In vitro studies corroborated that melatonin restrains the polarization of retina-specific T cells towards Th17 and Th1 cells in addition to enhancing the proportion of Treg cells. Pretreatment of retina-specific T cells with melatonin failed to induce EAU in naïve recipients. Furthermore, the ROS/ TXNIP/ HIF-1α pathway was shown to mediate the therapeutic effect of melatonin in EAU. Conclusions Melatonin regulates autoimmune T cells by restraining effector T cells and facilitating Treg generation, indicating that melatonin could be a hopeful treatment alternative for autoimmune uveitis.

scholarly journals Superantigenic Staphylococcus aureus Stimulates Production of Interleukin-17 from Memory but Not Naive T Cells

2009 ◽  
Vol 78 (1) ◽  
pp. 381-386 ◽  
Author(s):  
Ulrika Islander ◽  
Annica Andersson ◽  
Erika Lindberg ◽  
Ingegerd Adlerberth ◽  
Agnes E. Wold ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
T Cells ◽  
Th17 Cells ◽  
Mononuclear Cells ◽  
Memory T Cells ◽  
Inflammatory Diseases ◽  
Commensal Bacteria ◽  
Interleukin 17 ◽  
T Helper ◽  
T Helper 17

ABSTRACT T-helper 17 (Th17) cells are characterized by their production of interleukin-17 (IL-17) and have a role in the protection against infections and in certain inflammatory diseases. Humans who lack Th17 cells are more susceptible to Staphylococcus aureus infections compared to individuals having Th17 cells. S. aureus is part of the commensal skin microflora and also colonize the infant gut. To investigate whether UV-killed S. aureus would be more capable of inducing IL-17 than other commensal bacteria, we stimulated mononuclear cells from adults, infants, and newborns with various gram-positive and gram-negative commensal bacteria. IL-17 was produced from adult memory Th17 cells after stimulation with superantigen-producing S. aureus but not nonsuperantigenic S. aureus or other common commensal gut bacteria. Cells from newborns were poor IL-17 producers after stimulation with S. aureus, whereas in some cases IL-17 was secreted from cells isolated from infants at the age of 4 and 18 months. These results suggest that superantigenic S. aureus are particularly efficient in stimulating IL-17 production and that the cytokine is produced from memory T cells.

scholarly journals Electroacupuncture Improves Blood Pressure in SHRs by Regulating the Immune Balance between Th17 and Treg

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Yang Wang ◽  
Lili Zhang ◽  
Li Li ◽  
Hantong Hu ◽  
Pan Pan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Th17 Cells ◽  
Spontaneously Hypertensive Rats ◽  
Treg Cells ◽  
T Helper ◽  
Hypertensive Rats ◽  
T Helper 17 ◽  
Spontaneously Hypertensive ◽  
Immune Balance

The present study investigated the effects of electroacupuncture on blood pressure in spontaneously hypertensive rats (SHRs) by regulating the immune balance of T helper 17 cells (Th17 cells) and regulatory T cells (Treg cells). This study investigated the role of electroacupuncture in the immune balance of SHRs using Western blot, flow cytometry, and ELISA techniques. Electroacupuncture significantly improved blood pressure, downregulated the expression of RORγt, and upregulated the expression of Foxp3, reduced the production of Th17 cells, promoted the production of Treg cells, reduced the secretion of IL-6 and IL-17, and increased the secretion of TGF-β1 and IL-10. These findings suggest that electroacupuncture therapy effectively improved the systolic blood pressure of SHRs, and its mechanism may be related to promotion of the immune balance between Th17 and Treg.

scholarly journals Interleukin-23 Is Required for Development of Arthritis in Mice Vaccinated and Challenged with Borrelia Species

2008 ◽  
Vol 15 (8) ◽  
pp. 1199-1207 ◽  
Author(s):  
Nicholas J. Kotloski ◽  
Dean T. Nardelli ◽  
Sara Heil Peterson ◽  
Jose R. Torrealba ◽  
Thomas F. Warner ◽  
...  
Keyword(s):  
Lymph Node ◽  
Th17 Cells ◽  
Lyme Arthritis ◽  
T Helper ◽  
T Helper 17 ◽  
Survival Factor ◽  
Lymph Node Cells ◽  
Interleukin 23 ◽  
Insight Into

ABSTRACTWe recently hypothesized that T helper 17 (Th17) cells and their associated cytokines are involved in the development of arthritis following infection withBorrelia burgdorferi. Here, we show that interleukin-23 (IL-23), a survival factor for Th17 cells, is required for the induction of arthritis in mice vaccinated withB. burgdorferistrain 297 and challenged with “Borrelia bissettii.” WhenBorrelia-vaccinated and -challenged mice were given antibodies to the p19 subunit of IL-23, they failed to develop the histopathological changes observed in untreated vaccinated and challenged mice. In addition, viableB. bissettiiorganisms stimulated the secretion of IL-17 fromBorrelia-immune lymph node cells during in vitro culture. When anti-IL-23 p19 antibody was included in cultures ofB. bissettiiorganisms andBorrelia-immune lymph node cells, the production of IL-17 was reduced to levels observed in cultures containing immune cells alone. Taken together, these results support the hypothesis that Th17 cell-associated cytokines are involved in the development ofBorrelia-mediated arthritis. These findings provide insight into previously overlooked immune mechanisms responsible for the development of Lyme arthritis.

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