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 Effect of BDNF on Differentiation of Circulating Th17 and Treg Cells in SLE Patients and Exploration of Signal Transduction Pathways

2021 ◽  
Author(s):  
Bailing Tian ◽  
Xiaoyu Hou ◽  
Mengmeng Zhao
Keyword(s):  
Flow Cytometry ◽  
Lupus Erythematosus ◽  
Treg Cells ◽  
Signal Transduction Pathways ◽  
T Helper ◽  
Rt Pcr ◽  
Systemic Lupus ◽  
Bdnf Level ◽  
T Helper 17 ◽  
Serum Bdnf

Abstract Circulating brain-derived neurotrophic factor(BDNF) is mainly derived from lymphocytes. The serum BDNF level in SLE is decreased, and BDNF may be involved in the pathogenesis of systemic lupus erythematosus(SLE). Our aim is to determine whether BDNF affects the differentiation of CD4+T cells into regulatory T(Treg) or T helper 17(Th17). 30 patients were selected. TGF-β and IL-6 were added to induce differentiation of Treg and Th17. After co-cultured with BDNF, the percentages of CD4+CD25+CD127low and CD4+IL-17A+ were detected by Flow cytometry, and the expression of Foxp3mRNA and RORγtmRNA were detected by Rt-PCR. Under the condition of Th17 and Treg polarization, after co-cultured with BDNF and TrkB IgG, the phosphorylation of Akt, mTORC1 and ERK1/2 were detected by western-blot, the percentages of CD4+CD25+CD127low and CD4+IL-17A+ were detected by Flow cytometry. Under the condition of Th17 polarization, with the increase of BDNF concentration(60ng/ml, 120ng/ml, 350ng/ml), the percentages of CD4+IL-17A+ and the expression of RORγtmRNA were decreased(p<0.01; p<0.001). Under the condition of Treg polarization, the percentages of CD4+CD25+CD127low and the expression of Foxp3mRNA were increased(p<0.001). Regardless of Th17 or Treg polarization, the phosphorylation of Akt, mTORC1 and ERK1/2 in the BDNF group were reduced(p<0.001), and the phosphorylation of Akt, mTORC1 in the TrkBIgG group were enhanced(p<0.001). BDNF down-regulates the differentiation of Th17 and promotes the differentiation of Treg in SLE through inhibiting the activation of PI3K-Akt-mTORC1 axis and ERK1/2 pathway. BDNF could play a certain role in maintaining the balance of Treg/Th17 ratio in SLE.

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 Systemic Lupus Erythematosus with and without Anti-dsDNA Antibodies: Analysis from a Large Monocentric Cohort

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Conti Fabrizio ◽  
Ceccarelli Fulvia ◽  
Perricone Carlo ◽  
Massaro Laura ◽  
Marocchi Elisa ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Clinical Laboratory ◽  
Renal Involvement ◽  
Serum Levels ◽  
Activity Measurement ◽  
Systemic Lupus ◽  
Before And After ◽  
Dsdna Antibodies

Objectives. The anti-dsDNA antibodies are a marker for Systemic Lupus Erythematosus (SLE) and 70–98% of patients test positive. We evaluated the demographic, clinical, laboratory, and therapeutical features of a monocentric SLE cohort according to the anti-dsDNA status.Methods. We identified three groups: anti-dsDNA + (persistent positivity); anti-dsDNA ± (initial positivity and subsequent negativity during disease course); anti-dsDNA − (persistent negativity). Disease activity was assessed by the European Consensus Lupus Activity Measurement (ECLAM).Results. We evaluated 393 patients (anti-dsDNA +: 62.3%; anti-dsDNA ±: 13.3%; anti-dsDNA −: 24.4%). The renal involvement was significantly more frequent in anti-dsDNA + (30.2%), compared with anti-dsDNA ± and anti-dsDNA − (21.1% and 18.7%, resp.;P=0.001). Serositis resulted significantly more frequent in anti-dsDNA − (82.3%) compared to anti-dsDNA + and anti-dsDNA ± (20.8% and 13.4%, resp.;P<0.0001). The reduction of C4 serum levels was identified significantly more frequently in anti-dsDNA + and anti-dsDNA ± (40.0% and 44.2%, resp.) compared with anti-dsDNA − (21.8%,P=0.005). We did not identify significant differences in the mean ECLAM values before and after modification of anti-dsDNA status (P=0.7).Conclusion. Anti-dsDNA status influences the clinical and immunological features of SLE patients. Nonetheless, it does not appear to affect disease activity.

Increased CD4+CD25-Foxp3+ T cells in Chinese systemic lupus erythematosus: correlate with disease activity and organ involvement

Lupus ◽  
2018 ◽  
Vol 27 (13) ◽  
pp. 2057-2068 ◽  
Author(s):  
Z-J Yin ◽  
B-M Ju ◽  
L Zhu ◽  
N Hu ◽  
J Luo ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Cell Subset ◽  
Treg Cells ◽  
Organ Involvement ◽  
Systemic Lupus ◽  
Clinical Indicators ◽  
Disease States

Objective The increment of CD4+CD25−Foxp3+T cells has been reported in systemic lupus erythematosus (SLE) patients. However, the exact identity of this T cell subset is still unclear. Thus, we analyzed CD4+CD25−Foxp3+T cells and Treg cells (CD4+CD25+Foxp3+ T cells) in a large sample of Chinese SLE patients in different disease states. Methods A total of 280 SLE patients and 38 healthy volunteers were enrolled, which included 21 patients with untreated new-onset lupus (UNOL), 13 patients with drug withdrawal more than 6 months and 246 patients with treatments. Phenotypic and functional analysis of peripheral blood CD4+CD25−Foxp3+ T cells and Treg cells were performed by flow cytometry. The correlation of CD4+CD25−Foxp3+T cells and Treg cells with disease activity, clinical indicators and organ involvement were analyzed. Results CD4+CD25−Foxp3+ T cells and Treg cells were significantly increased in SLE patients and showed significantly positive correlations with disease activity. CD4+CD25−Foxp3+ T cells were significantly increased in patients with skin and hematologic involvement as well as arthritis. Diverse changes between CD4+CD25−Foxp3+ T cells and Treg cells when faced with different medications, especially HCQ and MMF. CD4+CD25−Foxp3+ T cells expressed more IFN-γ and less CTLA-4 than CD4+CD25+Foxp3+ T cells, which were similar to CD4+CD25+Foxp3− T cells, and expressed similar IL-17, ICOS and Helios to CD4+CD25+Foxp3+ T cells. The synthesis capacity of IL-10 of CD4+CD25−Foxp3+ T cells and the expression of GITR on CD4+CD25−Foxp3+ T cells were between CD4+CD25+Foxp3+ and CD4+CD25+Foxp3− T cells. Conclusions Our results indicate that increased CD4+CD25−Foxp3+ T cells in lupus patients, which combined the features of suppression and pro-inflammatory, may serve as a biomarker for disease activity and organ involvement in SLE.

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 T Helper 17/Regulatory T Cell Balance and Experimental Models of Peritoneal Dialysis-Induced Damage

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Georgios Liappas ◽  
Guadalupe Tirma Gónzalez-Mateo ◽  
Pedro Majano ◽  
José Antonio Sánchez- Tomero ◽  
Marta Ruiz-Ortega ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Experimental Models ◽  
T Helper ◽  
Peritoneal Fibrosis ◽  
T Helper 17 ◽  
Th17 Response ◽  
Mesenchymal Transition ◽  
Future Goals ◽  
Clinical Biomarkers ◽  
Cell Balance

Fibrosis is a general complication in many diseases. It is the main complication during peritoneal dialysis (PD) treatment, a therapy for renal failure disease. Local inflammation and mesothelial to mesenchymal transition (MMT) are well known key phenomena in peritoneal damage during PD. New data suggest that, in the peritoneal cavity, inflammatory changes may be regulated at least in part by a delicate balance between T helper 17 and regulatory T cells. This paper briefly reviews the implication of the Th17/Treg-axis in fibrotic diseases. Moreover, it compares current evidences described in PD animal experimental models, indicating a loss of Th17/Treg balance (Th17 predominance) leading to peritoneal damage during PD. In addition, considering the new clinical and animal experimental data, new therapeutic strategies to reduce the Th17 response and increase the regulatory T response are proposed. Thus, future goals should be to develop new clinical biomarkers to reverse this immune misbalance and reduce peritoneal fibrosis in PD.

A case of refractory lupus nephritis complicated by psoriasis vulgaris that was controlled with secukinumab

Lupus ◽  
2018 ◽  
Vol 27 (7) ◽  
pp. 1202-1206 ◽  
Author(s):  
Y Satoh ◽  
K Nakano ◽  
H Yoshinari ◽  
S Nakayamada ◽  
S Iwata ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Psoriasis Vulgaris ◽  
Tissue Sample ◽  
Interleukin 17 ◽  
T Helper ◽  
T Helper 17 ◽  
T Helper 17 Cells ◽  
Biopsy Tissue ◽  
Interleukin 17A

It has been reported that T helper 17 cells are involved in the pathogenesis of systemic lupus erythematosus, but there is no report on interleukin-17-targeted therapy. We report a case of a 62-year-old female who presented with psoriasis vulgaris and refractory lupus nephritis. Because her conditions were resistant to conventional treatment, and flow cytometry confirmed the proliferation of activated T helper 17 cells in peripheral blood, and examination of a renal biopsy tissue sample confirmed infiltration of numerous interleukin-17-positive lymphocytes to the renal interstitium, administration of the anti-interleukin-17A antibody secukinumab was initiated. After starting secukinumab the clinical and biological features were improved.

Sign in / Sign up

Export Citation Format

Share Document