scholarly journals Inflammatory Cytokine Neutralizing Antibody Treatment Could Recover Increased Follicular Helper and Follicular Regulatory T Cells in Murine Models of Arthritis

2021 ◽  
Author(s):  
Xingyue Zeng ◽  
Meng Li ◽  
Mohan Zheng ◽  
Tianci Liu ◽  
Rui Kang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Peripheral Blood ◽  
Neutralizing Antibody ◽  
Mouse Spleen ◽  
Inflammatory Factor ◽  
Antibody Treatment ◽  
Follicular Helper ◽  
Anti Inflammatory ◽  
And Function ◽  
The Impact

Abstract Objective. We aimed to illustrate the changes of follicular helper (TFH) and follicular regulatory (TFR) cells in rheumatoid arthritis using the collagen-induced arthritis (CIA) model and clarity the impact of anti-inflammatory treatment on TFH and TFR cells.Methods. We established 10-week-old CIA model and used flow cytometry to analyze the changes of TFH and TFR cells in peripheral blood and spleen at different time points (5w, 7w, 10w,13w). The expression of TIGIT, CD226, ICOS and PD-1 characterizing the functions of TFH and TFR were also analyzed. The function of spleen TFH and TFR cells from CIA was further analyzed. The effects of anti-inflammatory antibody treatments on the subpopulation and function changes of TFH and TFR were also analyzed in CIA mice.Results. The levels of TFH and TFR were significantly increased in spleen and peripheral blood of CIA mice. After treatment, TFH and TFR cells decreased significantly. TIGIT+ and TIGIT+CD226-TFH cells in CIA mouse spleen were elevated and PD-1 and ICOS expression on TFH and TFR cells in the spleen were also significantly increased. The ability of TFH to secrete IL-21 and help B cells, and TFR to secrete IL-10 and inhibit TFH were both enhanced in CIA mouse spleen. After antibody treatment, cell subsets and functions were significantly recovered.Conclusion. In the pathogenesis of rheumatoid arthritis, TFH and TFR cells in the germinal center increases and their functions are enhanced. After the treatment by inflammatory factor antibodies, TFH and TFR subsets and their functions can be significantly recovered.

scholarly journals Gene-regulatory network study of rheumatoid arthritis in single-cell chromatin landscapes of peripheral blood mononuclear cells

2021 ◽  
Author(s):  
Cantong Zhang ◽  
Xiaoping Hong ◽  
Haiyan Yu ◽  
Hongwei Wu ◽  
Huixuan Xu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Single Cell ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
High Resolution Map ◽  
The Impact ◽  
Accessible Chromatin

Abstract Rheumatoid arthritis is a chronic autoinflammatory disease with an elusive etiology. Assays for transposase-accessible chromatin with single-cell sequencing (scATAC-seq) contribute to the progress in epigenetic studies. However, the impact of epigenetic technology on autoimmune diseases has not been objectively analyzed. Therefore, scATAC-seq was performed to generate a high-resolution map of accessible loci in peripheral blood mononuclear cells (PBMCs) of RA patients at the single-cell level. The purpose of our project was to discover the transcription factors (TFs) that were involved in the pathogenesis of RA at single-cell resolution. In our research, we obtained 22 accessible chromatin patterns. Then, 10 key TFs were involved in the RA pathogenesis by regulating the activity of MAP kinase. Consequently, two genes (PTPRC, SPAG9) regulated by 10 key TFs were found that may be associated with RA disease pathogenesis and these TFs were obviously enriched in RA patients (p<0.05, FC>1.2). With further qPCR validation on PTPRC and SPAG9 in monocytes, we found differential expression of these two genes, which were regulated by eight TFs (ZNF384, HNF1B, DMRTA2, MEF2A, NFE2L1, CREB3L4 (var. 2), FOSL2::JUNB (var. 2), MEF2B). What is more, the eight TFs showed highly accessible binding sites in RA patients. These findings demonstrate the value of using scATAC-seq to reveal transcriptional regulatory variation in RA-derived PBMCs, providing insights on therapy from an epigenetic perspective.

scholarly journals The impact of non-pharmacological treatments for diseases of the locomotor system on the prescribed drug use and lifestyles of the patients in the sanatoria in Busko-Zdroj

2015 ◽  
Vol 28 (4) ◽  
pp. 273-277
Author(s):  
Milena Korczak ◽  
Jacek Owczarek
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
Drug Use ◽  
Pharmacological Treatments ◽  
Locomotor System ◽  
The Third ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
The Impact

Abstract The article is the result of research on the impact of non-pharmacological therapies for diseases of the locomotor system on the prescribed drug use and lifestyles of the patients of the sanatoria in Busko-Zdroj. The reported research uses primary and secondary measures. The former includes the assessment of the impact of non-pharmacological sanatorium treatments for locomotor system diseases on the use of prescribed drug regimes, while the latter is aimed at assessing the patients’ quality of life. The research was conducted on adult patients of both genders in the sanatoria in Busko-Zdroj. The subjects were patients suffering from disorders of the musculoskeletal system such as rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, osteoporosis and discopathies. The research included two visits, the first at the start of the research and the second at the end of the research. The patients were examined for a period of three consecutive weeks. The study involved 170 patients, 50% of them were women and 50% men. A decline in the use of painkillers and anti-inflammatory drugs makes a very interesting finding. After the first week, as many as 38% of the examined patients limited the use of painkillers and/or anti-inflammatory drugs. After the second week, 62% of the patients reduced the use of the drugs, and after the third week of treatment, up to 90% of the patients did so. The improvement of patients’ lives is noticeable in the psychological, physical and motor fields.

AB0043 THE IMBALANCE OF T FOLLICULAR REGULATORY CELL AND T FOLLICULAR HELPER CELL IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1324-1325
Author(s):  
R. Su ◽  
Y. Y. Wang ◽  
F. Y. Hu ◽  
X. Zheng ◽  
Y. Liu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Peripheral Blood ◽  
Control Group ◽  
Healthy Controls ◽  
Regulatory Cells ◽  
Regulatory Cell ◽  
Helper Cells ◽  
Follicular Helper ◽  
Healthy Control ◽  
T Follicular Helper Cell

Background:Rheumatoid arthritis (RA) is a chronic inflammatory disease which can lead to severe joint damage and disability.The relationship between antibodies and rheumatoid arthritis has long been well established. Recently, many studies have found that T follicular regulatory cells(Tfr) and T follicular helper cells (Tfh) are closely related to antibody generation on lymphoid follicular germinal centers (GCs)[1-2]. Tfr cells can inhibite the GC reaction and suppress production of high-affinity antibodies. The dysregulation of Tfh cells can lead to the production of autoantibodies by B cells.Objectives:To examine the expression of circulating T follicular regulatory cell (Tfr) and T follicular helper cell and its subsets(Tfh1 Tfh2 Tfh17) in RA patients and healthy control group.Methods:Level of Tfr and Tfh1,Tfh2 and Tfh17 cells in the peripheral blood of 17 new RA patients, 30 treated RA patients and 18 healthy controls were deceted by flow cytomery. All patients were hospitalised at the Department of Rheumatology, Second Hospital of Shanxi Medical University.Results:We found that the level of Tfr (CD3+CD4+CD25+CXCR5+FOP3+) percent(P=0.020), in the peripheral blood in RA patients were significantly decreased compared with healthy controls. The percent of Tfh (CD3+CD4+CXCR5+CD45RA-) (P=0.039)and Tfh17 (CD3+CD4+CXCR5+CD45RA-CXCR3-CCR6+) (P=0.000)were increased, but there are no statistical difference about Tfh1(CD3+CD4+CXCR5+CD45RA-CXCR3+CCR6-)(P=0.558) and Tfh2 (CD3+CD4+CXCR5+CD45RA-CXCR3-CCR6-) percent(P=0.079). We compared the above indicators between new and treated RA patients, and the results indicated that the Tfr(P=0.013),Tfh (P=0.002) and Tfh1(P=0.034) were significantly increased in the new RA patients compared to the treated RA patients, there were no differences between the two groups in Tfh2(P=0.419) and Tfh17 percent(P=0.124).Conclusion:Our results indicated that disorder of Tfr and Tfh subsets were involved in RA, restoring the Tfr/Tfh balance may be the potential therapeutic targets.Fig. 1.Comparison of Tfr, Tfh and its subsets(Tfh1 Tfh2 Tfh17) percent among the RA patients (n = 47) and healthy control group (n = 18) (*P < 0.05).Fig. 2.Comparison of Tfr,Tfh and its subsets(Tfh1 Tfh2 Tfh17) percent among the new RA patients (n = 17) and treated RA patients(n = 30) (*P < 0.05).References:[1]Deng J, Wei Y, Fonseca VR, Graca L, Yu D.T follicular helper cells and T follicular regulatory cells in rheumatic diseases[J].Nat Rev Rheumatol. 2019, 15(8):475-490.[2]Chen Liu, Dongwei Wang, Songsong Lu, et al.Increased Circulating Follicular Treg Cells Are Associated With Lower Levels of Autoantibodies in Patients With Rheumatoid Arthritis in Stable Remission.Arthritis Rheumatol. 2018, 70(5):711-721Disclosure of Interests:None declared

scholarly journals AB0044 ESTABLISHED RHEUMATOID ARTHRITIS PATIENTS HAVE INCREASED FREQUENCIES OF FOLLICULAR REGULATORY T CELLS IN PERIPHERAL BLOOD

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1325.3-1325
Author(s):  
C. Tomé ◽  
S. C. Barreira ◽  
P. Martins ◽  
A. Valido ◽  
R. Barros ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
T Cell Subsets ◽  
Peripheral Blood Mononuclear ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Healthy Donors ◽  
Cd69 Expression

Background:Several studies have demonstrated that an immune dysregulation affecting both B and T cells occurs in rheumatoid arthritis (RA). Follicular helper T (Tfh) cells are crucial for B cell maturation, activation and class-switching as well as for germinal center (GC) formation, whereas follicular regulatory T (Tfr) cells can modulate the GC reaction by suppressing Tfh and B cells.Objectives:The main goal of this study was to analyze the phenotype and frequency of circulating follicular T cell subsets in established RA patients.Methods:Blood samples were collected from established RA patients with active disease, treated with methotrexate (n=32) and from a group of age and sex-matched healthy donors (n=11). Peripheral blood mononuclear cells (PBMC) were isolated and Tfh (CD4+CXCR5+CD45RO+) and Tfr (CD4+ CXCR5+CD25+FoxP3+) cells, as well as their three major subsets [CXCR3+CCR6- (Th1-like), CXCR3-CCR6- (Th2-like) and CXCR3-CCR6+ (Th17-like)] were evaluated by flow cytometry.Results:The frequency of circulating Tfh cells was similar between established RA patients and controls. Nonetheless, RA patients had a decreased frequency of Th1-like Tfh cells, and an increased frequency of Th2-like Tfh cells when compared to controls. No significant differences were observed in the frequencies of Th17-like Tfh cells between both groups. The frequency of circulating Tfr cells was significantly increased in RA patients in comparison to controls. Furthermore, Tfr cells from RA patients had significantly increased CD69 median fluorescence intensity (MFI) values when compared to controls. No significant differences were found in the percentages and MFI values of PD-1, ICOS, CD28, CTLA-4, CD40-L and HLA-DR expressed by Tfh and Tfr cells in RA patients when compared to controls.Conclusion:Established RA patients have increased circulating frequencies of Tfr cells, with higher CD69 expression levels, when compared to healthy controls. These results suggest a pre-activation state of Tfr cells in RA and a potential role in the disease physiopathology.*RA Moura, JE Fonseca and L Graca are joint senior authors.Disclosure of Interests:None declared

scholarly journals Azithromycin alleviates the severity of rheumatoid arthritis via targeting UPR component GRP78

2021 ◽  
Author(s):  
Yongli Zhang ◽  
Luna Ge ◽  
Guanhua Song ◽  
Ruojia Zhang ◽  
Shufeng Li ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Expression Profiles ◽  
Regulatory Element ◽  
Gene Expression Profiles ◽  
Attractive Potential ◽  
Therapeutic Drug ◽  
Inflammatory Factor ◽  
Anti Inflammatory ◽  
Novel Target

Background and Purpose: Azithromycin (AZM) is a macrolide antibiotic with well-described anti-inflammatory properties. This study aimed to substantiate its treatment potential in rheumatoid arthritis (RA). Experimental Approach: Gene expression profiles were collected by RNA-sequencing and the effects of AZM were assessed in functional assays. In vitro and vivo assays for examining the blockade of glucose-regulated protein 78 (GRP78) actions by AZM: assays for defining the anti-inflammatory activity of AZM using fibroblast-like synoviocytes (FLSs) from RA patients as well as collagen-induced arthritis (CIA) in DBA/1 mice. Identification and characterization of the binding of AZM to GRP78 using drug affability responsive target stability assay, proteomics and cellular thermal shift assay. Detect AZM inhibition of GRP78 and dependence of AZM’s anti-arthritis activity on GRP78. Key Results: AZM reduced pro-inflammatory factor production, cell migration, invasion and chemo-attractive potential, enhanced apoptosis, thereby reducing the deleterious inflammatory response of RA FLSs in vitro. AZM ameliorated the severity of CIA lesions. Transcriptional analyses implied that AZM treatment causes impairments in signaling cascades associated with cholesterol and lipid biosynthetic process. GRP78 was isolated as a novel target of AZM. AZM-mediated activation of unfolded protein response (UPR) via inhibiting GRP78 activity is required not only for inducing the expression of C/EBP-homologous protein (CHOP), but also for activation of sterol-regulatory element binding protein (SREBP) and its targeted genes involved in cholesterol and lipid biosynthetic process. Further, deletion of GRP78 abolished AZM’s anti-arthritis activity. Conclusion and Implications: These findings confirmed that AZM is an anti-arthritis therapeutic drug for RA treatment.

scholarly journals Immunological Changes in Peripheral Blood of Ankylosing Spondylitis Patients during Anti-TNF-α Therapy and Their Correlations with Treatment Outcomes

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Rongjuan Chen ◽  
Hongyan Qian ◽  
Xiaoqing Yuan ◽  
Shiju Chen ◽  
Yuan Liu ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Treatment Response ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Regulatory B Cell ◽  
Follicular Helper ◽  
Tnf Α ◽  
The Difference ◽  
Factor Α ◽  
The Impact

Tumor necrosis factor-α (TNF-α) inhibitors are the main types of biological conventional synthetic disease-modifying antirheumatic drugs and have efficacy in treating ankylosing spondylitis (AS) which is not sensitive for nonsteroidal anti-inflammatory drug. However, the impact of TNF-α inhibitors on immune cells in patients with AS is still clearly undefined, and the impact of immune cells on treatment response is also largely elusive. This study is aimed at evaluating the longitudinal changes of circulating immune cells after anti-TNF-α therapy and their associations with treatment response in AS patients. Thirty-five AS patients receiving the treatment of anti-TNF-α therapy were included into this prospective observational study. The frequencies of immune cells including Th1, Th2, Th17, regulatory T cell (Treg), T follicular helper cell (Tfh), and regulatory B cell (Breg) in the peripheral blood were measured by flow cytometry at baseline and 4 time points after therapy. The difference in the circulating immune cells between responders and nonresponders was compared. This study suggested that anti-TNF-α therapy could significantly reduce circulating proinflammatory immune cells such as Th17 and Tfh, but significantly increased the percentages of circulating Treg and Breg. Moreover, circulating Breg may be a promising predictor of response to anti-TNF-α therapy in AS patients.

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