Elevated Th22 Cells Correlated with Th17 Cells in Patients with Rheumatoid Arthritis

Background

T-helper (Th) 22 and Th17 cells are implicated in the pathogenesis of autoimmune diseases. The roles of Th22 cells in the pathophysiology of rheumatoid arthritis (RA) remain unsettled.

Materials and Methods

CD4⁺IFN??^?IL17^?IL-22⁺ T cells (Th22 cells), CD4⁺IFN??^?IL-22^?IL17⁺ T cells (pure Th17 cells), CD4⁺IL17⁺ T cells (Th17 cells), and CD4⁺IFN??⁺ T cells (Th1 cells) in RA, osteoarthritis patients, and healthy controls were examined by flow cytometry. Plasma IL-22 and IL-17 levels were examined by enzyme-linked immunosorbent assay.

Results

Th22 cells, pure Th17 cells, Th17 cells, and interleukin-22 were significantly elevated in RA patients compared with osteoarthritis and healthy controls, but there were no significant differences regarding Th1 cells and interleukin-17. Th22 cells showed a positive correlation with interleukin-22 as well as pure Th17 cells or Th17 cells in RA patients. Additionally, the percentages of Th22 cells, pure Th17 cells as well as Th17 cells correlated positively with both C-reactive protein levels and 28-joints disease activity score.

Conclusion

Together, our results indicated a possible role of Th22 pure Th17 cells and Th17 cells in RA, and blockade of the interleukin-22 may be a reasonable therapeutic strategy for RA.     

Cardiovascular Risk in Rheumatoid Arthritis and Systemic Autoimmune Rheumatic Disorders: a Suggested Model of Preventive Strategy

The pathogenesis of accelerated cardiovascular damage commonly characterizing patients affected by systemic chronic inflammatory and autoimmune rheumatic disorders is quite complex and still not fully clarified. However, it is well accepted that a strong relationship between multiple factors, including both traditional cardiovascular risk factors and disease-related inflammatory and autoimmune mechanisms, may in part explain the precocious atherosclerotic vessel damage and the increased incidence of cardiovascular events. Nevertheless, although several recent studies focused their attention on the investigation of these complex mechanisms, data regarding possible preventive strategies aimed to reduce long-term cardiovascular risk in these subjects are still lacking and not conclusive. In this setting, the early introduction of evidence-based preventive measures for the correct management of patients with systemic autoimmune disorders would be of extreme importance to reduce subclinical atherosclerosis incidence and possible major cardiovascular events.     

Th1/Th2失衡对于类风湿性关节炎炎症损伤的临床意义

目的 探讨类风湿性关节炎患者外周血以及关节液中的Th1/Th2失衡对于类风湿性关节炎炎症损伤的意义.方法 采用酶联免疫法(ELISA)检测42例类风湿性关节炎(rheumatoid arthritis,RA)患者外周血以及关节液中的IL-2、IL-4、IL-6、IL-10、TNF-α以及IFN-γ的表达情况.同时选取我院就诊的35例健康体检人员作为对照组.结果 相比于对照组以及RA患者的外周血,RA患者的关节积液中的IL-2、IL-6以及IL-10、IL-4水平均明显升高;相比于对照组的外周血,RA患者的外周血以及关节积液中的IFN-γ以及TNF-α水平均明显升高;相比于对照组,RA患者关节积液中的IFN-γ/IL-4比例明显升高.抗环瓜氨酸抗体(cyclic citrullinated peptide,CCP)阳性的RA患者关节积液中IL-2、IL-6、IFN-γ以及TNF-α的表达水平均明显高于CCP阴性的RA患者,以上数据组间比较差异均有统计学意义,P＜0.05.结论 Th1/Th2失衡是引起RA炎症性损伤的重要免疫学机制,其诱导的免疫性炎症反应是主要表现,CCP抗体阳性患者的炎性损伤更加严重.     

CD6 as a Therapeutic Target in Autoimmune Diseases: Successes and Challenges

The transmembrane surface glycoprotein CD6 was one of the first antigens identified on T lymphocytes. The recognition of its involvement in T-cell signaling processes heralds the potential of CD6 as a target for therapy in a number of pathologies associated with imbalances in T-cell function. Its tissue distribution, cellular expression, and overall molecular structure are well described, and the interaction with its physiological ligand CD166 has been determined to the amino-acid level. Nevertheless, the involvement of CD6 in signaling pathways remains poorly characterized and its biological function is controversial; still unresolved are whether CD6 is a co-stimulatory molecule in T-cell activation or, similar to the related CD5 antigen, a modulator of intracellular signaling. Here we revisit the earliest attempts of modulating immune function using CD6 monoclonal antibodies, and review the current thinking behind the recent developments in immunotherapy targeting CD6. Notwithstanding the promises and hopes brought by monoclonals already in clinical trials, the fact is that very little is known about the mechanism of action of these reagents, whether they enhance the physiological role of the receptor or whether they may induce a completely novel biochemical response that might, nevertheless, be beneficially used to treat human immune pathology.     

Combined Treatment of Etanercept and MTX Reverses Th1/Th2, Th17/Treg Imbalance in Patients with Rheumatoid Arthritis

Objective  

To explore the mechanism of Etanercept in the treatment of rheumatoid arthritis (RA), we investigated whether the Th1/Th2 and Th17/regulatory T cells (Treg) imbalance could be reversed by Etanercept and whether the reversal was related to the improvement of clinical indications.     

Tumor Necrosis Factor Receptor Pre-Ligand Assembly Domain is an Important Therapeutic Target in Inflammatory Arthritis

Tumor necrosis factor (TNF)-alpha is an important proinflammatory cytokine and plays a crucial role in pathogenesis of inflammatory arthritis, such as rheumatoid and septic arthritis. TNFalpha exerts its effect by binding to the extracellular domain of TNF receptor (TNFR) 1 and 2. The amino-terminal portion of the TNFR extracellular domain, known as cysteine rich domain 1 (CRD1), or the pre-ligand binding assembly domain (PLAD), plays an important role in the TNFR signaling pathway. TNFR1 PLAD and TNFR2 PLAD proteins block the actions of TNFalpha by interfering with assembly of the receptor complex required for TNFalpha binding. The TNFR1 PLAD protein have been shown to significantly inhibit inflammatory arthritis, such as arthritis induced by TNFalpha, bacterial DNA, lipopolysaccharide, and collagen. The TNFR1 PLAD protein inhibit nuclear factor (NF)-kappaB activation and osteoclastogenesis triggered by TNFalpha was able to inhibit expression of receptor activator of NF-kappaB (RANK), RANK ligand, matrix metalloproteinase and inducible nitric oxide synthase in collagen-induced arthritis. The TNFR1 PLAD protein could therefore be useful in treatment of inflammatory arthritis.     

Autoimmune Th17 Cells Induced Synovial Stromal and Innate Lymphoid Cell Secretion of the Cytokine GM-CSF to Initiate and Augment Autoimmune Arthritis

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Trichostatin Differentially Regulates Th1 and Th2 Responses and Alleviates Rheumatoid Arthritis in Mice

Objective  

Histone deacetylase inhibitors have shown suppressive effects on tumor growth and in some autoimmune diseases. However, the molecular mechanisms of their effects are not very clear. The purpose of this study was to investigate the effects of trichostatin A (TSA) on collagen-induced rheumatoid arthritis (CIA) in a mouse model and its underlying mechanisms.     

Activin A: A Potential Therapeutic Target for Characterizing and Stopping Joint Pain Early in Rheumatoid Arthritis Patients

It is common for rheumatoid arthritis patients to suffer from persistent joint pain for decades during their lifetime. Activin A, a member of the transforming growth factor β superfamily, which plays a role in the very early phase of inflammatory processes, can also induce pain behaviors. In view of the contribution of synovial inflammation to the progression of rheumatoid arthritis, here we present the hypothesis that activin A may be a potential therapeutic target, serving as a marker for joint pain in which inflammatory processes are involved and as a target for early intervention.     

IL-23/Th17轴与自身免疫性疾病

既往研究认为,自身免疫性疾病主要是Th1/Th2平衡失调所致,但就Th1细胞亚群的研究结果并不能完全解释自身免疫性疾病的发病机制.Th17细胞是新发现的CD4+辅助性T细胞亚群,IL-23是Th17细胞赖以存在,并维持其稳态及扩增,促进其分泌IL-17的必需细胞因子.目前认为,越来越多的研究表明,IL-23/Th17轴参与了多种自身免疫性疾病的病理过程.     

活动期类风湿关节炎患者血清及关节液白细胞介素-17水平变化及与有关实验室指标的关系

目的:分析类风湿关节炎(RA)患者外周血和关节液中T辅助细胞17(Thl7)相关细胞因子白介素-17(IL-17)水平,探讨其在RA中的变化特点及与实验室指标的相关性.方法:用ELISA检测50例活动期RA患者血清和其中15例关节液以及30例正常人血清IL-17水平.同时测定RA患者血清超敏C反应蛋白(hs-CRP)、...     

P2X7 Receptor Signaling Pathway as a Therapeutic Target for Neurodegenerative Diseases

A recent study suggested that neuroinflammation plays a major role in the pathogenesis of a number of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Although the precise mechanism is obscure, dysregulation of the signaling transduction pathway in microglia may enhance inflammation, leading to synaptic dysfunction and ultimately to neuronal cell death. The expression and function of the P2X7 receptor (P2X7R), an ATP-gated ion channel abundantly expressed in microglia in the brain, is significantly up-regulated in the postmortem brain of Alzheimer’s disease patients and various neurodegenerative disease animal models. This supports the role of the P2X7R pathway in the progression of neurodegeneration. Blocking P2X7R using brilliant blue G, a P2X7R antagonist that can cross the blood–brain barrier, has been shown to result in the amelioration of neuropathology in various animal models. Taken together, these results raise the possibility that the P2X7R signaling pathway could be a therapeutic target for treating various neurodegenerative diseases.