Electroacupuncture Attenuates Collagen-Induced Arthritis in Rats through Vasoactive Intestinal Peptide Signalling-Dependent Re-Establishment of the Regulatory T Cell/T-Helper 17 Cell Balance

2015 ◽  
Vol 33 (4) ◽  
pp. 305-311 ◽  
Author(s):  
Jun Zhu ◽  
Xiao-Yi Chen ◽  
Lian-Bo Li ◽  
Xin-Tong Yu ◽  
Yin Zhou ◽  
...  
Keyword(s):  
Treg Cell ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Treg Cells ◽  
T Helper ◽  
Collagen Induced Arthritis ◽  
T Helper 17 ◽  
Cell Frequency ◽  
Cell Balance ◽  
Vip Receptor

Objective Imbalance between T-helper 17 (Th17) cells and regulatory T (Treg) cells is causally linked to the development of rheumatoid arthritis (RA). In this study, we tested the hypothesis that electroacupuncture (EA) confers therapeutic benefits in RA through activation of vasoactive intestinal peptide (VIP)-dependent signalling and restoration of the Th17/Treg cell balance. Materials and Methods A collagen-induced arthritis (CIA) model was induced in Sprague–Dawley rats by injection of bovine type II collagen in incomplete Freund's adjuvant on day 0 and day 7. Three days after the second injection, EA was given at acupuncture points GB39 and ST36 three times per week for 4 weeks. To block VIP signalling, [D-P-Cl-Phe(6)-Leu(17)]-VIP, a VIP receptor antagonist, was administered intraperitoneally 30 min before EA. Inflammatory and pathological responses in the joint were assessed. Synovial VIP receptor mRNA levels and Treg and Th17 cell frequencies in the spleen were determined. Results EA significantly reduced the severity of CIA, as evidenced by reduced paw volumes, arthritis scores and inflammation scores. EA significantly increased mRNA expression of the VIP receptor VPAC1 and led to an elevation in CD4+FOXP3+ Treg cell frequency and a reduction in CD4+IL17+ Th17 cell frequency. Pre-injection of a VIP receptor antagonist significantly reversed EA-induced expansion of Treg cells, but did not alter the frequencies of Th17 cells. Conclusions EA exerts anti-inflammatory effects in a collagen-induced rat model of arthritis. These effects appear to be mediated through activation of VIP signalling and re-establishment of the Th17/Treg cell balance.

scholarly journals Pivotal Roles of T-Helper 17-Related Cytokines, IL-17, IL-22, and IL-23, in Inflammatory Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Ning Qu ◽  
Mingli Xu ◽  
Izuru Mizoguchi ◽  
Jun-ichi Furusawa ◽  
Kotaro Kaneko ◽  
...  
Keyword(s):  
Th17 Cell ◽  
Th17 Cells ◽  
Functional Role ◽  
Inflammatory Diseases ◽  
Interleukin 17 ◽  
T Helper ◽  
T Helper 17 ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

T-helper 17 (Th17) cells are characterized by producing interleukin-17 (IL-17, also called IL-17A), IL-17F, IL-21, and IL-22 and potentially TNF-α and IL-6 upon certain stimulation. IL-23, which promotes Th17 cell development, as well as IL-17 and IL-22 produced by the Th17 cells plays essential roles in various inflammatory diseases, such as experimental autoimmune encephalomyelitis, rheumatoid arthritis, colitis, and Concanavalin A-induced hepatitis. In this review, we summarize the characteristics of the functional role of Th17 cells, with particular focus on the Th17 cell-related cytokines such as IL-17, IL-22, and IL-23, in mouse models and human inflammatory diseases.

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 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.

Restoring T-helper 17 cell/regulatory T-cell balance and decreasing disease activity by rapamycin and all-trans retinoic acid in patients with systemic lupus erythematosus

Lupus ◽  
2019 ◽  
Vol 28 (12) ◽  
pp. 1397-1406 ◽  
Author(s):  
Y Chu ◽  
C Zhao ◽  
B Zhang ◽  
X Wang ◽  
Y Wang ◽  
...  
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Treg Cells ◽  
T Helper ◽  
T Helper 17 ◽  
Sledai Score ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Before And After ◽  
Cell Balance

Objective This study aimed to investigate the effect of rapamycin (RAPA) alone or in combination with all-trans retinoic acid (ATRA) on the T-helper 17 (Th17) cell/regulatory T-cell (Treg) balance in patients with systemic lupus erythematosus (SLE) and to evaluate the clinical efficacy. Methods Seventy patients with SLE were enrolled. They were randomly and equally divided into RAPA and RAPA + ATRA groups. The number of Th17 and Treg cells was measured by flow cytometry before and after treatment for 6, 12 and 24 weeks. The SLE Disease Activity Index (SLEDAI) score and the prednisone dose before and after treatment were used to evaluate the efficacy between the two groups. Results In both groups, at different time points after treatment, the number of Th17 cells ( p = 0.003) and Th17/Treg ratio ( p = 0.044) reduced, while the number of Treg cells ( p = 0.574) tended to increase. The SLEDAI score and the dose of prednisone decreased significantly ( p < 0.001). There was no significant difference in the number of Th17 cells ( p = 0.089), Treg cells ( p = 0.059), Th17/Treg ratio ( p = 0.580), SLEDAI score ( p = 0.127) and the dose of prednisone ( p = 0.329) between the two groups. Conclusion Disease activity in SLE patients reduced with RAPA alone or in conjunction with ATRA, reducing glucocorticoid requirement. One of its mechanisms of action may be regulating the Th17/Treg cell balance, which provides a new model for the pathogenesis and potential treatment of SLE.

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 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 Expression of tyrosine hydroxylase in CD4+ T cells contributes to alleviation of Th17/Treg imbalance in collagen-induced arthritis

2016 ◽  
Vol 241 (18) ◽  
pp. 2094-2103 ◽  
Author(s):  
Xiao-Qin Wang ◽  
Yan Liu ◽  
Huan-Huan Cai ◽  
Yu-Ping Peng ◽  
Yi-Hua Qiu
Keyword(s):  
T Cells ◽  
Tyrosine Hydroxylase ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Treg Cells ◽  
Cytokine Expression ◽  
Gene Knockdown ◽  
Gene Overexpression ◽  
Collagen Induced Arthritis ◽  
Ankle Joints

Tyrosine hydroxylase (TH), a rate-limiting enzyme for the synthesis of catecholamines, is expressed in T lymphocytes. However, the role of T cell-expressed TH in rheumatoid arthritis (RA) is less clear. Herein, we aimed to show the contribution of TH expression by CD4+ T cells to alleviation of helper T (Th)17/regulatory T (Treg) imbalance in collagen-induced arthritis (CIA), a mouse model of RA. CIA was prepared by intradermal injection of collagen type II (CII) at tail base of DBA1/J mice. Expression of TH in the spleen and the ankle joints was measured by real-time polymerase chain reaction and Western blot analysis. Percentages of TH-expressing Th17 and Treg cells in splenic CD4+ T cells were determined by flow cytometry. Overexpression and knockdown of TH gene in CD4+ T cells were taken to evaluate effects of TH on Th17 and Treg cells in CIA. TH expression was upregulated in both the inflamed tissues (spleen and ankle joints) and the CD4+ T cells of CIA mice. In splenic CD4+ T cells, the cells expressing TH were increased during CIA. These cells that expressed more TH in CIA were mainly Th17 cells rather than Treg cells. TH gene overexpression in CD4+ T cells from CIA mice reduced Th17 cell percentage as well as Th17-related transcription factor and cytokine expression and secretion, whereas TH gene knockdown enhanced the Th17 cell activity. In contrast, TH gene overexpression increased Treg-related cytokine expression and secretion in CD4+ T cells of CIA mice, while TH gene knockdown decreased the Treg cell changes. Collectively, these findings show that CIA induces TH expression in CD4+ T cells, particularly in Th17 cells, and suggest that the increased TH expression during CIA represents an anti-inflammatory mechanism.

Th17 cells: A prognostic marker for MS rebound after natalizumab cessation?

2016 ◽  
Vol 23 (1) ◽  
pp. 114-118 ◽  
Author(s):  
Jürgen Haas ◽  
Katharina Schneider ◽  
Alexander Schwarz ◽  
Mirjam Korporal-Kuhnke ◽  
Simon Faller ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Prognostic Marker ◽  
Peripheral Blood ◽  
Th17 Cell ◽  
Th17 Cells ◽  
T Helper ◽  
T Helper 17 ◽  
Blood Samples ◽  
Cytokine Levels

Background: Multiple sclerosis (MS) patients are at risk of renewed disease activity after discontinuing natalizumab (NAT) treatment. Objective: Assessing the implication of T helper 17 (Th17) cells in MS reactivation after NAT cessation. Methods: We monitored frequencies of Th17 cells and interleukin (IL)-17 cytokine levels in blood samples of 57 MS patients, without, during, and after NAT exposure. Results: Frequencies of both Th17 cells and, in part, also IL-17 levels, in peripheral blood increased under prolonged NAT therapy, returned to baseline after NAT withdrawal and became almost undetectable in blood samples of individuals who experienced relapses during the wash-out phase. Conclusion: Assessing the Th17-cell/IL-17 axis might help to predict rebound MS activity after NAT withdrawal.

scholarly journals RORα enforces stability of the T-helper-17 cell effector program

2020 ◽  
Author(s):  
June-Yong Lee ◽  
Jason A. Hall ◽  
Maria Pokrovskii ◽  
Lina Kroehling ◽  
Lin Wu ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Th17 Cell ◽  
Th17 Cells ◽  
T Helper ◽  
T Helper 17 ◽  
Enhancer Element ◽  
Peripheral Tissues ◽  
Th17 Cell Differentiation

SummaryT helper 17 (Th17) cells regulate mucosal barrier defenses, but also promote multiple autoinflammatory diseases. Although many molecular determinants of Th17 cell differentiation have been described, the transcriptional programs that sustain Th17 cells in vivo remain obscure. The transcription factor RORγt is critical for Th17 cell differentiation, but a distinct role of the closely-related RORα, which is co-expressed in Th17 cells, is not known. Here we demonstrate that, although dispensable for Th17 cell differentiation, RORα governs optimal Th17 responses in peripheral tissues. Thus, the absence of RORα in T cells led to significant reductions in both RORγt expression and effector function amongst Th17 cells, due to need for cooperative RORα and RORγt binding to a newly-identified Rorc enhancer element that is essential for Th17 lineage maintenance in vivo. Altogether, these data point to a non-redundant role of RORα in Th17 lineage maintenance via reinforcement of the RORγt transcriptional program.

Development of a Modified Skin Explant Assay to Study Treg Suppression of Th17 Cell Mediated GvHD in the Skin

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5434-5434
Author(s):  
Raewyn Broady ◽  
Sarah Q. Crome ◽  
Jessie Yu ◽  
Jan P Dutz ◽  
Megan K Levings
Keyword(s):  
T Cells ◽  
Treg Cell ◽  
Tissue Damage ◽  
Cd4 T Cells ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Acute Gvhd ◽  
Treg Cells ◽  
Haematopoietic Stem Cell ◽  
Graft Versus Host

Abstract Acute graft versus host disease (aGVHD) following haematopoietic stem cell transplantation (HCT) occurs when donor T cells infused with the graft recognise and react to histo-incompatible recipient antigens causing tissue damage. Historically, the inflammatory response in aGVHD was attributed to alloreactive CD4+ T helper and CD8+ cytotoxic T cells and alterations in cytokine production. Recently, a new CD4+ T cell subset, characterised by IL-17 production has been identified. TH17 cells produce high levels of proinflammatory cytokines, including IL-17A, IL-17F, and IL-22, and have been implicated in solid organ rejection and more recently a number of murine studies suggest that Th17 cells play a role in the development of aGVHD. It is well known that FOXP3+ regulatory T cells (Tregs) are critical for the maintenance of self-tolerance, and control the immune response to alloantigens. Murine studies have shown that adoptive transfer of these cells can prevent acute GVHD whereas selective depletion leads to an increased severity. In humans, Tregs also appear to control acute GVHD as they occur at a lower frequency in the peripheral blood patients with aGVHD compared to patients without GVHD. These findings have led to active interest into the use of these cells to prevent or decrease GVHD following allogeneic HCT. It has been reported that in vitro, Th17 cells are resistant to Treg cell mediated suppression of proliferation and IL-17 production, suggesting that the effector functions of Th17 cells might not be susceptible to Treg-cell-mediated inhibition. If true, this would suggest that Treg-based therapies might not be effective at limiting Th17-cell-mediated tissue damage. However, there is currently no evidence regarding whether Treg cells affect the phenotype or function of Th17 cells in tissues. Understanding the interactions between suppressive Tregs and pro-inflammatory T effectors in tissues that are targets of aGVHD, such as the skin, is critical to better define the potential of Tregs as adoptive therapy for the prevention or treatment of aGVHD. In order to address this question, we developed two methods to generate human Th17 cells, one based on over-expression of RORC2 and the other on sorting CCR4+CCR6+CD4+ T cells. We found that ectopic expression of RORC induces a cytokine and chemokine receptor profile analogous to in vivo differentiated Th17 cells. Although expression of RORC2 made CD4+ T cells resistant to Treg-cell mediated suppression of proliferation and IL-17 production, production of IFN-g, TNF-a and IL-6 could be suppressed in these Th17-like cells. In order to further delineate the functional consequence of the interaction between Treg and Th17 cells in tissues we developed a modified the human skin explant model that involves culture of 4 mm punch biopsies of skin with ex vivo Th17 cells (CCR4+CCR6+CD4+ T cells), RORC2 transduced CD4+ T cells, or controls, in the presence or absence of Treg and grading the graft-versus-host reactivity (grades I–IV) histopathologically. Preliminary data suggest that Th17 cells cause significant tissue destruction in this skin explant model, and experiments are ongoing to determine whether Treg cells can counteract these effects.

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