scholarly journals Dopamine Induces IL-6–Dependent IL-17 Production via D1-Like Receptor on CD4 Naive T Cells and D1-Like Receptor Antagonist SCH-23390 Inhibits Cartilage Destruction in a Human Rheumatoid Arthritis/SCID Mouse Chimera Model

2011 ◽  
Vol 186 (6) ◽  
pp. 3745-3752 ◽  
Author(s):  
Kazuhisa Nakano ◽  
Kunihiro Yamaoka ◽  
Kentaro Hanami ◽  
Kazuyoshi Saito ◽  
Yasuyuki Sasaguri ◽  
...  

Blood ◽  
2002 ◽  
Vol 100 (13) ◽  
pp. 4550-4556 ◽  
Author(s):  
Frederique Ponchel ◽  
Ann W. Morgan ◽  
Sarah J. Bingham ◽  
Mark Quinn ◽  
Maya Buch ◽  
...  

Rheumatoid arthritis (RA) is a chronic, inflammatory disease of the synovium of uncertain pathogenesis. A number of phenotypic and functional T-cell defects have been described in RA, including abnormal clonal expansions and suppressed proliferative responses, which suggest a defect in T-cell differentiation. Here, we show that RA patients possess fewer naive CD4+ T cells than healthy controls. Furthermore, a smaller proportion of these cells contains a T-cell receptor excision circle (TREC). Patients with RA also have unusual populations of T cells. These include immature cells characterized as CD45RBbrightCD45RA+CD62L− by flow cytometry and a large population that coexpresses CD45RA and CD45RO. These cells are hyperresponsive to mitogen and TCR stimulation when compared to naive cells. Additionally, an unusual putative central memory subset expressing CD62L, but not CD45RA, appears in RA patients at the expense of more typical cells. Levels of C-reactive protein correlate inversely with the TREC content of naive T cells and positively with the sizes of naive and immature atypical T-cell subsets. These data suggest that inflammation drives proliferation of naive T cells in RA and encourages their differentiation into atypical, hyperresponsive progeny. TREC content of individual naive and atypical T-cell subsets suggests an ontogeny consistent with this hypothesis. These studies provide further evidence of a T-cell differentiation defect in RA, which could explain some of the well-characterized immunologic features of the disease.



2020 ◽  
Vol 11 ◽  
Author(s):  
Kari Guderud ◽  
Line H. Sunde ◽  
Siri T. Flåm ◽  
Marthe T. Mæhlen ◽  
Maria D. Mjaavatten ◽  
...  




2001 ◽  
Author(s):  
A Skapenko ◽  
J Wendler ◽  
PE Lipsky ◽  
JR Kalden ◽  
H Schulze-Koops


2021 ◽  
Vol 12 ◽  
Author(s):  
Jana Heim ◽  
Giovanni Almanzar ◽  
Marc Schmalzing ◽  
Michael Gernert ◽  
Hans-Peter Tony ◽  
...  

IL-9-producing Th9 cells display a group of helper T cells with similarities to Th17 and Th2 T cells and have been shown to be involved in synovial inflammation in rheumatoid arthritis (RA) patients. So far, it is unclear which parameters drive Th9 differentiation in lymphocytes derived from RA patients compared to immunologically healthy individuals and whether autocrine mechanisms are able to enhance Th9 polarization. Further, parallel pathways of induction of IL-17-producing cells with Th9 phenotype have to be distinguished from exclusively Th9-inductive mechanisms. Thus, the present study aimed to determine the parameters of Th9 induction by simulation in a standardized inflammatory cytokine milieu.Peripheral naive and non-naive T cells of RA patients and healthy donors (HD) were cultured under Th9 and Th17-driving conditions and phenotypically analyzed by flow cytometry and molecular analysis.Our findings indicate a similar differentiation pathway of Th9 and Th17 cells and similar distributions of IL-9+ T cells in RA and HD regardless of Th9- or Th17-promoting cytokine milieus. Whereas the magnitude and direction of Th9- or Th17-polarization was about the same in RA and HD, IL-17+ CD4+ T cells were significantly stimulated by Th17-inducing conditions in HD. In conclusion, the results indicate that Th9- and Th17-inducing cytokine conditions mimicking autoimmune inflammation in RA may have similar stimulatory effects regarding polarization of peripheral naive and non-naive T cells into Th9 or Th17 cells. The results suggest that the differentiation of Th9 cells may be also induced by Th17-driving conditions.



2021 ◽  
Vol 23 (4) ◽  
pp. 725-730
Author(s):  
E. A. Blinova ◽  
L. V. Grishina ◽  
A. E. Sizkov ◽  
V. A. Kozlov

Much attention of researchers is directed to study the role of factors of homeostatic proliferation in the pathogenesis of autoimmune diseases, however, the effect of IL-7 and IL-15 on the phenotype of naive T cells  has not yet been sufficiently investigated in the pathology. The aim of this study was to investigate the proportion of CD45RA+ and CD31+ naive cells among CD4+ and CD8+ lymphocytes from healthy individuals and patients with rheumatoid arthritis (RA) upon stimulation with IL-7, IL-15 in vitro. In peripheral blood, we did not find any differences in the number of CD45RA+ and CD31+ cells between the group of donors and group of RA patients. In donors, stimulation by a combination of IL-7 with IL-15 promoted an increase in the proportion of CD4+CD45RA+ and CD8+CD45RA+  relative to their level in the peripheral blood. Whereas in RA patients the number of CD8+CD45RA+ cells decreased under IL-15 and the combination of IL-15 with IL-7 compared to the control without stimulation, and it, as a proportion of CD4+CD45RA+ cells, significantly differed from the content of these cells  under the same conditions in donors. There were no significant differences in the content of CD31+ cells and the number of CD31+ cells proliferating to cytokines, both between the groups of donors and patients with RA, and between different culture conditions. Thus, we can say that under the factors of homeostatic proliferation, there is a proportional increase in CD31+ T cells number, both in donors and in patients with RA. At the same time, naive T cells from donors  retain the expression of CD45RA during cultivation, while naive T cells from patients partially lose it. The obtained data  indicate that in RA, under  factors of  homeostatic proliferation  the phenotype of naive T cells is converted into the phenotype of memory T cells.



2017 ◽  
Vol 69 (3) ◽  
pp. 550-559 ◽  
Author(s):  
Brooke Rhead ◽  
Calliope Holingue ◽  
Michael Cole ◽  
Xiaorong Shao ◽  
Hong L. Quach ◽  
...  


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