scholarly journals IL-18 binding protein suppresses IL-17-induced osteoclastogenesis and rectifies type 17 helper T cell / regulatory T cell imbalance in rheumatoid arthritis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hong Ki Min ◽  
Sehee Kim ◽  
Ji-Yeon Lee ◽  
Kyoung-Woon Kim ◽  
Sang-Heon Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Differentiation ◽  
T Cell ◽  
Mononuclear Cells ◽  
Binding Protein ◽  
T Cell Differentiation ◽  
Dependent Manner ◽  
Helper T Cell ◽  
Expression Levels ◽  
Dose Dependent

Abstract Background Patients with rheumatoid arthritis (RA) have increased levels of interleukin-18 (IL-18) and decreased levels of IL-18 binding protein (IL-18BP) in the serum and synovial fluid (SF) compared to those in patients with osteoarthritis (OA) or in healthy controls. In this study, we evaluated the effects of IL-18BP on osteoclastogenesis and T cell differentiation in RA in vitro. Methods Serum and SF of patients with RA and OA were collected to compare IL-18 and IL-18BP levels by the enzyme-linked immunosorbent assay. Peripheral blood mononuclear cells (PBMCs) and SF mononuclear cells (SFMCs) of RA patients were cultured under type 17 helper T cell (Th17) polarisation conditions with or without IL-18BP. In addition, PBMCs were cultured in the presence of receptor activator of nuclear factor kappa-Β ligand (RANKL) or IL-17A with or without IL-18BP, and tartrate-resistant acid phosphatase (TRAP) staining and real-time quantitative polymerase chain reaction for expression levels of osteoclast-related genes were performed. Results IL-18 levels were higher in the serum and SF of patients with RA, whereas IL-18BP was lower in the SF of patients with RA than in the control group. Treatment of patients’ PBMCs with IL-18BP decreased the differentiation of CD4+ IL-17A+ and CD4+ RANKL+ T cells, whereas the differentiation of CD4+CD25highFOXP3+ T cell population increased in a dose-dependent manner. These changes in CD4+ T cell differentiation were also observed in the SFMCs of patients with RA. The levels IL-17A and soluble RANKL in the culture medium were significantly decreased by IL-18BP. IL-18BP administration decreased TRAP+ cell counts in a dose-dependent manner on the background of stimulation with RANKL-and IL-17A. In addition, expression levels of TRAP, NFATC1, CTSK, and TNFRSF11A (RANK) genes were lower in the IL-18BP treated cells. Conclusion We showed that IL-18BP can rectify the Th17/Treg imbalance and decrease IL-17-induced osteoclastogenesis in PBMCs from patients with RA. Therefore, IL-18BP may have therapeutic potential for RA treatment.

scholarly journals Follicular Helper T Cell Differentiation Requires Continuous Antigen Presentation that Is Independent of Unique B Cell Signaling

Immunity ◽  
2010 ◽  
Vol 33 (2) ◽  
pp. 241-253 ◽  
Author(s):  
Elissa K. Deenick ◽  
Anna Chan ◽  
Cindy S. Ma ◽  
Dominique Gatto ◽  
Pamela L. Schwartzberg ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Cell Signaling ◽  
B Cell ◽  
Antigen Presentation ◽  
T Cell Differentiation ◽  
Helper T Cell ◽  
B Cell Signaling ◽  
Follicular Helper ◽  
Follicular Helper T Cell

Function of CD27 in helper T cell differentiation

2011 ◽  
Vol 136 (2) ◽  
pp. 177-186 ◽  
Author(s):  
Sten Libregts ◽  
Ronald W. van Olffen ◽  
Koenraad F. van der Sluijs ◽  
Rene A.W. van Lier ◽  
Martijn A. Nolte
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
T Cell Differentiation ◽  
Helper T Cell

Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis

Blood ◽  
2002 ◽  
Vol 100 (13) ◽  
pp. 4550-4556 ◽  
Author(s):  
Frederique Ponchel ◽  
Ann W. Morgan ◽  
Sarah J. Bingham ◽  
Mark Quinn ◽  
Maya Buch ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Large Population ◽  
Chronic Inflammatory Disease ◽  
T Cell Differentiation ◽  
T Cell Subsets ◽  
Naive T Cells ◽  
Naïve T Cells

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.

scholarly journals Proteomic Profiling of Mouse Helper T Cell Differentiation

PROTEOMICS ◽  
2019 ◽  
Vol 19 (7) ◽  
pp. 1800045
Author(s):  
Henk‐Jan den Ham ◽  
Nadine A. Binai ◽  
Fatiha Zaaraoui‐Boutahar ◽  
Albert J. R. Heck ◽  
Arno C. Andeweg
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
T Cell Differentiation ◽  
Proteomic Profiling ◽  
Helper T Cell

scholarly journals Effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin on T Cell Differentiation in Primary Biliary Cholangitis

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Chunhui She ◽  
Jing Wang ◽  
Ning Tang ◽  
Zhaoyang Liu ◽  
Lishan Xu ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Autoimmune Disease ◽  
Mononuclear Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
T Cell Differentiation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Primary Biliary Cholangitis ◽  
Tetrachlorodibenzo P Dioxin

Exposure to dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is reported to affect the autoimmune system and increase the risk of autoimmune disease. Generally, dioxin exerts its toxicity via aryl hydrocarbon receptor (AhR). Primary biliary cholangitis (PBC) is a chronic autoimmune disease, and its pathogenesis involves the interplay between immune and environmental factors. This study showed the effect of dendritic cells (DCs) activated by TCDD on naïve CD4+ T cell differentiation in patients with PBC. CD14+ mononuclear cells were isolated from peripheral blood mononuclear cells (PBMCs) of patients with PBC and healthy people by magnetic cell separation and introduced into DCs. Two days after stimulation by TCDD, DCs were cocultured with naïve CD4+ T cells in a ratio of 1 : 2 for 3 days. Then, differentiation-related factors for naïve CD4+ T cells were detected by real-time fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and flow cytometry. The results showed that TCDD-activated DCs could promote Th1 and Th17 differentiation in patients with PBC. Therefore, this study demonstrated TCDD as an AhR agonist in regulating naïve CD4+ T cell differentiation in patients with PBC.

scholarly journals Capicua deficiency induces autoimmunity and promotes follicular helper T cell differentiation via derepression of ETV5

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Sungjun Park ◽  
Seungwon Lee ◽  
Choong-Gu Lee ◽  
Guk Yeol Park ◽  
Hyebeen Hong ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
T Cell Differentiation ◽  
Helper T Cell ◽  
Follicular Helper ◽  
Follicular Helper T Cell
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