scholarly journals Methotrexate restores the function of peripheral blood regulatory T cells in psoriasis vulgaris via the CD73/AMPK/mTOR pathway

2018 ◽  
Vol 179 (4) ◽  
pp. 896-905 ◽  
Author(s):  
K. Yan ◽  
W. Xu ◽  
Y. Huang ◽  
Z. Zhang ◽  
Q. Huang ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Peripheral Blood ◽  
Psoriasis Vulgaris ◽  
Mtor Pathway

scholarly journals Regulatory T Cells Fail to Suppress Fast Homeostatic Proliferation In Vitro

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 245
Author(s):  
Daniil Shevyrev ◽  
Valeriy Tereshchenko ◽  
Elena Blinova ◽  
Nadezda Knauer ◽  
Ekaterina Pashkina ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Autoimmune Diseases ◽  
Peripheral Blood ◽  
Treg Cells ◽  
Homeostatic Proliferation ◽  
Suppressive Activity ◽  
Healthy Donors

Homeostatic proliferation (HP) is a physiological process that reconstitutes the T cell pool after lymphopenia involving Interleukin-7 and 15 (IL-7 and IL-15), which are the key cytokines regulating the process. However, there is no evidence that these cytokines influence the function of regulatory T cells (Tregs). Since lymphopenia often accompanies autoimmune diseases, we decided to study the functional activity of Tregs stimulated by HP cytokines from patients with rheumatoid arthritis as compared with that of those from healthy donors. Since T cell receptor (TCR) signal strength determines the intensity of HP, we imitated slow HP using IL-7 or IL-15 and fast HP using a combination of IL-7 or IL-15 with anti-CD3 antibodies, cultivating Treg cells with peripheral blood mononuclear cells (PBMCs) at a 1:1 ratio. We used peripheral blood from 14 patients with rheumatoid arthritis and 18 healthy volunteers. We also used anti-CD3 and anti-CD3 + IL-2 stimulation as controls. The suppressive activity of Treg cells was evaluated in each case by the inhibition of the proliferation of CD4+ and CD8+ cells. The phenotype and proliferation of purified CD3+CD4+CD25+CD127lo cells were assessed by flow cytometry. The suppressive activity of the total pool of Tregs did not differ between the rheumatoid arthritis and healthy donors; however, it significantly decreased in conditions close to fast HP when the influence of HP cytokines was accompanied by anti-CD3 stimulation. The Treg proliferation caused by HP cytokines was lower in the rheumatoid arthritis (RA) patients than in the healthy individuals. The revealed decrease in Treg suppressive activity could impact the TCR landscape during lymphopenia and lead to the proliferation of potentially self-reactive T cell clones that are able to receive relatively strong TCR signals. This may be another explanation as to why lymphopenia is associated with the development of autoimmune diseases. The revealed decrease in Treg proliferation under IL-7 and IL-15 exposure can lead to a delay in Treg pool reconstitution in patients with rheumatoid arthritis in the case of lymphopenia.

mTOR pathway regulates the differentiation of peripheral blood Th2/Treg cell subsets in patients with pemphigus vulgaris

2021 ◽  
Author(s):  
Kuan Lai ◽  
Wenjing Zhang ◽  
Songshan Li ◽  
Zhiwen Zhang ◽  
Shuangde Xie ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Pemphigus Vulgaris ◽  
Treg Cells ◽  
Mtor Pathway ◽  
Cd4 T Cell ◽  
Cell Ratio ◽  
Loss Of Balance

Abstract Pemphigus vulgaris (PV) is a chronic and potentially life-threatening autoimmune blistering disease. Aberrant mTOR pathway activity is involved in many autoimmune diseases. This study investigated the correlation of mTOR pathway (PI3K/AKT/mTOR/p70S6K) activity with the loss of balance in T helper 2/regulatory T (Th2/Treg) cells in the peripheral blood of PV patients. CD4+ T cells were isolated from 15 PV patients and 15 healthy controls (HCs), the ratios of Th2/CD4+ T cells and Treg/CD4+ T cells, the activity of the mTOR pathway (PI3K/AKT/mTOR/p70S6K), the transcription factors and cytokines of Th2 and Treg cells were detected. Primary CD4+ T cells from PV patients were cultured under Th2- or Treg-polarizing conditions with or without rapamycin in vitro. We found that PV patients showed significantly elevated serum IL-4 when compared with HCs, and serum IL-4 level was positively correlated with the titer of anti-Dsg1/3 antibody and disease severity, while the serum TGF-β level was negatively correlated with the titer of anti-Dsg3 antibody and disease severity. Meanwhile, PV patients showed increased Th2/CD4+ T cell ratio; decreased Treg/CD4+ T cell ratio; elevated mRNA of PI3K, AKT, mTOR and protein of PI3K (P85), AKT, p-AKT (Ser473), mTOR, p-mTOR (Ser2448), p-p70S6K (Thr389), GATA3; reduced protein of forkhead box protein 3. Rapamycin inhibited Th2 cell differentiation and promoted Treg cell differentiation in vitro. These data suggest a close association between mTOR pathway activation and the loss of balance in Th2/Treg cells in peripheral blood of PV patients. Inhibiting mTORC1 can help restore the Th2/Treg balance.

scholarly journals Sublingual immunotherapy increases Treg/Th17 ratio in allergic rhinitis

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 826-832
Author(s):  
Jiarong Wang ◽  
Liansheng Qiu ◽  
Yimin Chen ◽  
Minyun Chen
Keyword(s):  
T Cells ◽  
Allergic Rhinitis ◽  
Retrospective Study ◽  
Regulatory T Cells ◽  
Visual Analog Scale ◽  
Peripheral Blood ◽  
Sublingual Immunotherapy ◽  
Analog Scale ◽  
Vas Score ◽  
Medication Score

Abstract Background Few studies investigated the effects of sublingual immunotherapy (SLIT) on the peripheral regulatory T cells (Tregs)/Th17 ratio. Objective To investigate the effectiveness of SLIT in children with allergic rhinitis (AR) and the effects on the Tregs/Th17 ratio. Methods This was a retrospective study of children who were treated for AR between April 2017 and March 2018 at one hospital. The patients were grouped according to the treatments they received: SLIT + pharmacotherapy vs pharmacotherapy alone. Results Eighty children (51 boys and 29 girls; 40/group) were included. The visual analog scale (VAS) and medication scores at 1 year in the SLIT + pharmacotherapy group were 2.70 ± 1.08 and 1.1 ± 0.8, respectively, which were lower than at baseline (7.7 ± 1.2 and 3.6 ± 1.0, respectively) (both Ps < 0.05). For the pharmacotherapy group, the VAS score was decreased at 1 year vs baseline (3.3 ± 1.2 vs 7.4 ± 1.0; P < 0.05), but the medication score did not change (P > 0.05). In the SLIT + pharmacotherapy group, the Treg percentage increased, while the Th17 percentage decreased at 1 year (both Ps < 0.01). The percentages of Tregs and Th17s did not change in the pharmacotherapy group (both Ps > 0.05). Conclusions SLIT + pharmacotherapy can increase the Treg percentage and decrease the Th17 percentage in the peripheral blood of children with AR.

scholarly journals Isolation of functional human regulatory T cells (Treg) from the peripheral blood based on the CD39 expression

2009 ◽  
Vol 346 (1-2) ◽  
pp. 55-63 ◽  
Author(s):  
Magis Mandapathil ◽  
Stephan Lang ◽  
Elieser Gorelik ◽  
Theresa L. Whiteside
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Peripheral Blood

Expansion of CD4+CD25+FOXP3+ Regulatory T Cells in Peripheral Blood and Skin Lesions of Patients with Atopic Dermatitis

2008 ◽  
Vol 121 (2) ◽  
pp. S15-S15
Author(s):  
Y ITO ◽  
T MAKINO ◽  
Y ADACHI ◽  
H HIGASHIYAMA ◽  
T SHIMIZU ◽  
...  
Keyword(s):  
T Cells ◽  
Atopic Dermatitis ◽  
Regulatory T Cells ◽  
Peripheral Blood ◽  
Skin Lesions

Low Frequency of Regulatory T Cells in the Peripheral Blood of Children with Type 1 Diabetes Diagnosed under the Age of Five

2012 ◽  
Vol 60 (4) ◽  
pp. 307-313 ◽  
Author(s):  
Agnieszka Szypowska ◽  
Anna Stelmaszczyk-Emmel ◽  
Urszula Demkow ◽  
Włodzimierz Łuczyński
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Regulatory T Cells ◽  
Peripheral Blood ◽  
Low Frequency

Detection of CD4+CD25+FOXP3+ regulatory T cells in peripheral blood of patients with chronic autoimmune urticaria

2010 ◽  
Vol 52 (3) ◽  
pp. e15-e18 ◽  
Author(s):  
Ren-Shan Sun ◽  
Jian-Feng Sui ◽  
Xiao-Hong Chen ◽  
Xin-Ze Ran ◽  
Zi-Feng Yang ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Peripheral Blood ◽  
Autoimmune Urticaria
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