The role of T helper type 17 cells in inflammatory arthritis (original) (raw)

Role of Th17 cells in the pathogenesis of rheumatoid arthritis

World Journal of Rheumatology, 2013

Core tip: identification of interleukin-17-producing cells (Th17) rise as important source of inflammatory cytokines, IL-17 in particular, with critical role during inflammatory diseases.In this paper, we reviewed the differentiation of these cells from naive lymphocytes, their role during inflammatory arthritis and therapeutic tools to control these cells. Boniface K, Moynet D, Mossalayi MD. Role of Th17 cells in the pathogenesis of rheumatoid arthritis. World J Rheumatol 2013; 3(3): 25-31 Available from: URL

[Role of Th17 cells in rheumatoid arthritis]

Orvosi hetilap, 2010

The aim of this study was to quantify the number of T-helper (TH)-17 cells present in rheumatoid arthritis (RA) synovial fluid (SF) and to determine the level of interleukin (IL)-17 cytokine in RA, osteoarthritis (OA) and normal synovial tissue, as well as to examine SF macrophages for the presence of IL-23, IL-27 and interferon (IFN)-γ.

T helper 17 cells and interleukin-17 in patients with rheumatoid arthritis

International Journal of Clinical Rheumatology, 2019

International Journal of Clinical Rheumatology Research Article T helper 17 cells and interleukin-17 in patients with rheumatoid arthritis Rheumatoid Arthritis (RA) is one of the most prevalent autoimmune disease which may lead to a shorter life expectancy and lessened personal satisfaction. it is driven by effector T cells, particularly Th17 cells which possess a proinflammatory activity via the production of potent proinflammatory molecules IL-17. We aimed to assess and find possible correlations between the 28-joint Disease Activities Scores (DAS28), Th17 cells frequencies and IL-17 serum levels, and evaluation of the effect of anti-rheumatic therapy on Th17 cells and IL-17 levels. The frequencies of the circulating Th17 cells and serum levels of IL-17 were quantified using flow cytometry analysis and ELISA, respectively, in RA patients both before (baseline) and four months after anti-rheumatic therapy. Th17 cells in Peripheral Blood (PB) and serum IL-17 were found to be significantly increased in RA patients than in controls. The frequencies of circulating Th17 cells, the serum level of IL-17, and DAS28 score showed significant decline after therapy, the circulating Th17 cells, the serum levels of IL-17 were positively correlated with DAS28, also Th17 cells significantly correlated with serum IL-17. This study demonstrated increased level of Th-17 cells and serum IL-17 in RA indicating a role in pathogenesis and disease activity.

Role of TH-17 Cells in Rheumatic and Other Autoimmune Diseases

Rheumatology : Current Research, 2011

In humans multiple pathways can induce TH-17 cell differentiation, whereas in mice this process is mostly modulated by IL-6 and TGF-β. IL-17 produced by TH-17 cells has been associated with a number of inflammatory autoimmune diseases including psoriasis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, and rheumatoid arthritis. In this review, we have primarily focused on the role of TH-17 cells/IL-17 in the pathogenesis of rheumatoid arthritis and experimental arthritis. The potential role of TH-17 cells in rheumatoid arthritis progression has been demonstrated by correlating the percent TH-17 cells or levels of IL-17 with rheumatoid arthritis disease activity score and C-reactive protein levels. Further, previous studies suggest that IL-17 mediated vascularization may lay the foundation for rheumatoid arthritis joint neutrophil and monocyte recruitment as well as cartilage and bone destruction. The profound role of IL-17 in the pathogenesis of experimental arthritis may be due to its synergistic effect with TNF-α and IL-1β. Although the initial clinical trial employing anti-IL-17 antibody has been promising for rheumatoid arthritis, future studies in humans will shed more light on how anti-IL-17 therapy affects rheumatoid arthritis and other autoimmune disease pathogenesis.

The role of Th17 lymphocytes in pathogenesis of autoimmune arthritides

Polish Journal of Public Health, 2014

Th17 cells are newly described population of lymphoctyes, that recruits neutrophils to the site of inflammation and activate inflammatory phenotype of various tissues. They also play a pivotal role in autoimmune diseases and cancers. These cells secrete mainly different isoforms of IL-17, but also IL-21 and IL-22. Rheumatoid arthritis and juvenile idiopathic arthritis are the most common autoimmune joints’ inflammatory disease, affecting respectively adults and children. For a long time the immunopathogenesis of autoimmune diseases has been associated with Th1 lymphocytes. This hypothesis has changed after the discovery of Th17 cells, which are thought to be key mediators of autoimmune arthritides

Are Th17 Cells an Appropriate New Target in the Treatment of Rheumatoid Arthritis?

Clinical and Translational Science, 2010

Discovery of Th 17 cells Until about a decade ago, many human autoimmune diseases and the corresponding experimental animal models had been viewed as being driven by Th 1 cells. However, immunologists encountered a dilemma when they realized that experimental autoimmune encephalomyelitis (EAE: a mouse model of multiple sclerosis) and collagen-induced arthritis (CIA: a mouse model of rheumatoid arthritis) both were aggravated by the absence of Th 1 associated cytokines, receptors or transcription factors, such as IFN-γ, IFN-γ receptor, IL-12 p35, IL-12 receptor ␤ 2, or Stat1. 1-5 However, mice lacking the IL-12p40 subunit, which is found not only in IL-12 but also in IL-23, were resistant to these diseases, and IL-23p19 knockout mice were shown to be protected from EAE 6 and CIA. 7 Th is paradox was resolved in 2005 by a discovery of new subset of CD4+ T cells that produce IL-17A and IL-17F, expand in response to IL-23, and induce EAE and CIA upon adoptive transfer in mice. 8-10 Th ese lymphocytes, termed Th 17 cells, are characterized by expression of RORγt as a master regulator gene as well as secretion of IL-17A, IL-17F, IL-21, and IL-22. Th 17 cells are crucial in host defense against extracellular bacteria and some fungi, which Th 1 and Th 2 immunity are not fully eff ective against, and also play essential roles in many autoimmune or infl ammatory diseases, both in mice and humans (Table 1). 11-13 Discussion What is the connection between Th 17 cells and rheumatoid arthritis? Multiple lines of evidence indicate that Th 17 cells are important in rheumatoid arthritis (RA). As summarized in Table 2 , IL-17 activates a diverse array of cell types that participate in the pathogenesis of RA, including synovial fi broblasts, monocytes, macrophages, chondrocytes, and osteoblasts. IL-17 induces production of proinfl ammatory cytokines, such as TNF, IL-1, IL-6, IL-23, which amplify positive feedback loops that commit naïve CD4 T cells to the Th 17 lineage. 14-16 By inducing chemokine production, IL-17 indirectly attracts numerous eff ector T cells, B cells, monocytes, and neutrophils to the infl amed joint. 17 Of note, acting in synergy with TNF and IL-1-β, IL-17 induces CCL20, 18 which strongly attracts lymphocytes, including Th 17 cells that express CCR6, a receptor for CCL20. In bone, IL-17 stimulates osteoblasts to express receptor activator of nuclear factor kappa-B ligand (RANKL). 19 Such osteoblasts then activate osteoclasts that express RANK as a membrane receptor. Th is interaction leads to bone resorption. Finally, induction of matrix metalloproteinases (MMPs) 20 and vascular endothelial growth factor (VEGF) 21 are crucial in tissue destruction and angiogenesis, respectively. Brief overview of Th 17 diff erentiation in mice In mice, the combination of TGF-β and IL-6 or IL-21 induces Th 17 cells. 22-24 IL-6 or IL-21 phosphorylates Stat3, which induces RORγt expression. 25 Stat3 and RORγt appear to cooperate with each other 26 and bind to the IL-17 promoter to induce IL-17 expression. 27,28 TGF-β induces not only RORγt but also FoxP3 (master regulator gene of regulatory T cells: Tregs), 23,29,30 which physically associates with RORγt as well as Runx1. 28,29 In the absence of proinfl ammatory cytokines, FoxP3, through interaction with Runx1, inhibits RORγt-directed IL-17 expression, which is crucial in maintaining homeostasis of the immune network through generation of Tregs. 28,29 However, in the presence of proinfl ammatory cytokines, Stat3 and IRF4 both play essential roles in IL-6/21-and IL-6-mediated down-regulation of FoxP3, respectively, 31,32 aft er which RORγt primarily cooperates with Runx1 to induce IL-17. 28 In this manner, IL-6 or IL-21 play a pivotal role in tipping the balance toward Th 17, but not Treg diff erentiation by inhibiting TGF-β−mediated FoxP3 expression. 23,29 IL-21 produced by Th 17 cells in the presence of TGF-β induces Th 17 cells, creating an autoamplifi cation loop for Th 17 diff erentiation. 26,33,34 Th us, IL-21 might play a crucial role in maintaining a precursor pool of Th 17 cells when the supply of IL-6 is limited. Both IL-6 and IL-21, in cooperation with TGF-β, induce expression of the IL-23 receptor in a Stat3-26 and RORγt-dependent 33 fashion. Stat4, which has been viewed to be primarily essential for IL-12 signaling for Th 1 lineage commitment, was shown to also be important for IL-23-mediated expression of IL-17 in CD4 T cells in vitro. 35

Type 17 T helper cells—origins, features and possible roles in rheumatic disease

Nature Reviews Rheumatology, 2009

The differentiation of mouse T H 17 cells requires transforming growth factor β and iL-6, whereas human naive T cells can develop into T H 17 cells in the presence of iL-1β and iL-23 alone, transforming growth factor β having an indirect role in their development via the selective inhibition of T H 1 cell expansion. in both mice and humans, a late developmental plasticity of T H 17 cells towards the T H 1 lineage has been shown. Mainly based on mouse gene knockout studies, T H 17 lymphocytes have been found to have a pathogenic role in several autoimmune disorders; however, whether human autoimmune disorders, including rheumatoid arthritis (rA) and psoriasis, are prevalently T H 1-mediated or T H 17-mediated, is still unclear. research suggests that both T H 1 and T H 17 cells are involved in rA pathogenesis, raising the possibility that interventions that target both the iL-23-iL-17 (T H 17) and the iL-12-interferon γ (T H 1) axes might be successful future therapeutic approaches for rA.