scholarly journals Influence of the shared epitope on the elicitation of experimental autoimmune arthritis biomarkers

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250177
Author(s):  
Anastasios Karydis ◽  
Indra Sandal ◽  
Jiwen Luo ◽  
Amanda Prislovsky ◽  
Amanda Gamboa ◽  
...  
Keyword(s):  
Immune Response ◽  
Environmental Factors ◽  
Bone Loss ◽  
Th17 Cells ◽  
Shared Epitope ◽  
Periodontal Pathogen ◽  
Mouse Serum ◽  
Complex Nature ◽  
Autoimmune Arthritis ◽  
Experimental Autoimmune

Our previous studies have shown that inoculation of the oral cavity of “humanized” B6.DR1/4 mice with the periodontal pathogen Porphyromonas gingivalis results in an increase in the percentage of circulating Th17 cells, loss of bone and an exacerbation of experimental autoimmune arthritis. The aim of this study was to assess the role played by the human HLA-DRβ molecule containing the shared epitope supplied as a transgene to I-A˚ (murine class II null) C57BL/6 (B6) mice in driving these findings. We compared various immune response parameters as well as alveolar and peri-articular bone loss between humanized B6.DR1 (or B6.DR4) mice and their WT (B6) counterparts. We found that the presence of the shared epitope in the context of inoculation with P. gingivalis enhanced the percentage of Th17 cells generated, dramatically enhanced bone loss and importantly allowed for the generation of CCP2⁺ ACPAs that are not found in C57BL/6 or DBA/1 arthritic mouse serum. Due to the exceedingly complex nature of environmental factors impacting on genetic elements, it has been difficult to unravel mechanisms that drive autoimmune arthritis in susceptible individuals. The findings in this study may provide one small piece of this puzzle that can help us to better understand part of this complexity.

scholarly journals Bazedoxifene Regulates Th17 Immune Response to Ameliorate Experimental Autoimmune myocarditis via Inhibition of STAT3 Activation

2021 ◽  
Vol 11 ◽  
Author(s):  
Jing Wang ◽  
Tianshu Liu ◽  
Xiongwen Chen ◽  
Qiaofeng Jin ◽  
Yihan Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Th17 Cells ◽  
Specific Treatment ◽  
Inflammatory Factors ◽  
Autoimmune Myocarditis ◽  
Cardiac Inflammation ◽  
Inflammatory Heart Disease ◽  
Stat3 Signaling ◽  
Experimental Autoimmune Myocarditis ◽  
Experimental Autoimmune

Myocarditis is a type of inflammatory cardiomyopathy that has no specific treatment. Accumulating evidence suggests that Th17 cells play a prominent role in the pathogenesis of myocarditis. Interleukin-(IL)-6-mediated signal transducer and activation of transcription 3 (STAT3) signaling is essential for Th17 cell differentiation and secretion of inflammatory cytokines. Bazedoxifene inhibits IL-6/STAT3 signaling in cancer cells, but its effect on the Th17 immune response induced by myocarditis remains unknown. Here we explore the effect of Bazedoxifene on Th17 immune response and cardiac inflammation in a mouse model of experimental autoimmune myocarditis, which has been used to mimic human inflammatory heart disease. After eliciting an immune response, we found Bazedoxifene ameliorated cardiac inflammatory injury and dysfunction. Th17 cells and related inflammatory factors in splenic CD4+ T cells at day 14 and in the heart at day 21 were increased, which were reduced by Bazedoxifene. Furthermore, Bazedoxifene could regulate autophagy induction in polarized Th17 cells. In conclusion, Bazedoxifene affected STAT3 signaling and prevented cardiac inflammation deterioration, so may provide a promising therapeutic strategy for the treatment of experimental autoimmune myocarditis (EAM).

Coenzyme Q10 suppresses Th17 cells and osteoclast differentiation and ameliorates experimental autoimmune arthritis mice

2015 ◽  
Vol 166 (2) ◽  
pp. 92-102 ◽  
Author(s):  
JooYeon Jhun ◽  
Seung Hoon Lee ◽  
Jae-Kyeong Byun ◽  
Jeong-Hee Jeong ◽  
Eun-Kyung Kim ◽  
...  
Keyword(s):  
Coenzyme Q10 ◽  
Th17 Cells ◽  
Osteoclast Differentiation ◽  
Autoimmune Arthritis ◽  
Experimental Autoimmune

The Effects of D-aspartate on Neurosteroids, Neurosteroid Receptors, and Inflammatory Mediators in Experimental Autoimmune Encephalomyelitis

2019 ◽  
Vol 19 (3) ◽  
pp. 316-325
Author(s):  
Mahdi Goudarzvand ◽  
Yaser Panahi ◽  
Reza Yazdani ◽  
Hosein Miladi ◽  
Saeed Tahmasebi ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Inflammatory Mediators ◽  
Mouse Serum ◽  
Enzyme Linked Immunosorbent Assay ◽  
Oral Gavage ◽  
Autoimmune Encephalomyelitis ◽  
Beneficial Effects ◽  
17Β Estradiol ◽  
The Brain ◽  
Experimental Autoimmune

Objective: Experimental autoimmune encephalomyelitis (EAE) is a widely used model for multiple sclerosis. The present study has been designed to compare the efficiencies of oral and intraperitoneal (IP) administration of D-aspartate (D-Asp) on the onset and severity of EAE, the production of neurosteroids, and the expression of neurosteroid receptors and inflammatory mediators in the brain of EAE mice. Methods: In this study, EAE was induced in C57BL/6 mice treated with D-Asp orally (D-Asp-Oral) or by IP injection (D-Asp-IP). On the 20th day, brains (cerebrums) and cerebellums of mice were evaluated by histological analyses. The brains of mice were analyzed for: 1) Neurosteroid (Progesterone, Testosterone, 17β-estradiol) concentrations; 2) gene expressions of cytokines and neurosteroid receptors by reverse transcription polymerase chain reaction, and 3) quantitative determination of D-Asp using liquid chromatography-tandem mass spectrometry. Further, some inflammatory cytokines and matrix metalloproteinase-2 (MMP-2) were identified in the mouse serum using enzyme-linked immunosorbent assay kits. Results: Our findings demonstrated that after D-Asp was administered, it was taken up and accumulated within the brain. Further, IP injection of D-Asp had more beneficial effects on EAE severity than oral gavage. The concentration of the testosterone and 17β-estradiol in D-Asp-IP group was significantly higher than that of the control group. There were no significant differences in the gene expression of cytokine and neurosteroid receptors between control, D-Asp-IP, and D-Asp-Oral groups. However, IP treatment with D-Asp significantly reduced C-C motif chemokine ligand 2 and MMP-2 serum levels compared to control mice. Conclusion: IP injection of D-Asp had more beneficial effects on EAE severity, neurosteroid induction and reduction of inflammatory mediators than oral gavage.

Experimental Autoimmune Prostatitis: Dihydrotestosterone Influence Over the Immune Response

2003 ◽  
Vol 170 (6) ◽  
pp. 2486-2489 ◽  
Author(s):  
GUSTAVO P. DISERIO ◽  
EDGAR NOWOTNY
Keyword(s):  
Immune Response ◽  
Experimental Autoimmune

CCDC134 ameliorated experimental autoimmune encephalomyelitis by suppressing Th1 and Th17 cells

2018 ◽  
Vol 71 ◽  
pp. 158-168 ◽  
Author(s):  
Peng Xia ◽  
Xiaoting Gong ◽  
Lin Xiao ◽  
Yida Wang ◽  
Tianzhuo Zhang ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Th17 Cells ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

scholarly journals T Helper Type 17 Immune Response Plays an Indispensable Role for Development of Iodine-Induced Autoimmune Thyroiditis in Nonobese Diabetic-H2h4 Mice

Endocrinology ◽  
2009 ◽  
Vol 150 (11) ◽  
pp. 5135-5142 ◽  
Author(s):  
Ichiro Horie ◽  
Norio Abiru ◽  
Yuji Nagayama ◽  
Genpei Kuriya ◽  
Ohki Saitoh ◽  
...  
Keyword(s):  
Immune Response ◽  
Autoimmune Thyroiditis ◽  
Th17 Cells ◽  
Intermediate Phenotype ◽  
Lymphocyte Infiltration ◽  
Wild Type ◽  
T Helper ◽  
Nonobese Diabetic ◽  
Th2 Immune Response ◽  
Helper Type

T helper type 1(Th1)/Th2 paradigm has been expanded by discovery of a novel effector T cell (Teff) subset, Th17 cells, which produce a proinflammatory cytokine IL-17. Th17 cells have recently been shown to play a major role in numerous autoimmune diseases that had previously been thought to be Th1-dominant diseases. We here studied the significance of Th17 cells in iodine-induced autoimmune thyroiditis in nonobese diabetic-H2h4 mice, a mouse model of Hashimoto’s thyroiditis in humans, which spontaneously develop antithyroglobulin autoantibodies and intrathyroidal lymphocyte infiltration when supplied with iodine in the drinking water. We observed increased numbers of Th1 and Th17 cells in spleen and accumulation of both types of Teff in the thyroid glands of iodine-fed wild-type mice, indicating that Th17 cells as well as Th1 cells constitute thyroid lesions. Furthermore, the incidence and severity of intrathyroidal lymphocyte infiltration, and the titers of antithyroglobulin autoantibodies were markedly reduced in iodine-treated IL-17−/− mice as compared with wild-type mice. Of interest, IL-17+/− mice showed an intermediate phenotype. Therefore, the present study, together with a previous report demonstrating the importance of Th1, not Th2, immune response for developing thyroiditis using mice deficient for interferon-γ or IL-4, clearly indicates that both Th1 and Th17 cells are critical Teff subsets for the pathogenesis of spontaneous autoimmune thyroiditis in nonobese diabetic-H2h4 mice.

Ursodeoxycholic acid attenuates experimental autoimmune arthritis by targeting Th17 and inducing pAMPK and transcriptional corepressor SMILE

2017 ◽  
Vol 188 ◽  
pp. 1-8 ◽  
Author(s):  
Eun-Jung Lee ◽  
Jeong-Eun Kwon ◽  
Min-Jung Park ◽  
Kyung-Ah Jung ◽  
Da-Som Kim ◽  
...  
Keyword(s):  
Ursodeoxycholic Acid ◽  
Autoimmune Arthritis ◽  
Transcriptional Corepressor ◽  
Experimental Autoimmune
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