According to this article whats the role of TNF in Rheumatoid Arthritis. Expand on how the signaling pathway is disrupted in your answer. J Clin Transl RJ Clin TranslJ Clin Transl Res. 2016 Nov 10; 2(3): 84-90.Published online 2016 Sep 15.The role of TNF-α in rheumatoid arthritis: a focus on regulatory T cellsMark Farrugia¹ and Byron Baron▸ Author information Article notes ▸ Copyright and License information DisclaimerAbstractPMCID: PMC6410649PMID: 30873466Go to: ▸The autoimmune disorder rheumatoid arthritis (RA) causes chronic inflammation and destruction of joints.T cells are a predominant component of the synovial environment in RA, however the functional role ofthese cells is not yet fully understood. This is in part due to the fact that the balance and importance of therelation of Tregs with T-effector cells in RA is still under investigation. The current treatment regimen forthis debilitating disease focuses on controlling symptoms and preventing further joint damage through theuse of therapies which affect different areas of the immune system at the synovium. One of the maintherapies involves Tumor Necrosis Factor alpha (TNF-α) inhibitors. In the RA immune-environment, TNF-a has been shown to have an influential and extensive but as yet poorly understood effect on Treg function invivo, and undoubtably an important role in the treatment of RA. Interestingly, the high levels of TNF-αfound in RA patients appear to interfere with the mechanisms controlling the suppressive function of Tregs-1. IntroductionRelevance for patients: This review focuses on the conflicting literature available regarding the role playedby Tregs in RA and the impact of TNF-α and anti-TNF-α therapies on Tregs in this scenario. Individualssuffering from RA can benefit from better insight of the treatment mechanisms of the immunologicprocesses which occur throughout this disease, as current treatments for RA focus on several different areasof the immune system at the synovial compartment.Keywords: rheumatoid arthritis, regulatory T cells, TNF-α therapy, joint inflammationGo to: ►Rheumatoid arthritis (RA) is an autoimmune disorder that manifests itself as a chronic inflammation of thelining of the joints, with significant morbidity and mortality rates if left untreated [1]. RA is characterizedby synovial inflammation and hyperplasia (swelling), autoantibody production (rheumatoid factor (RF) andanti-citrullinated protein antibody (AC-PA)), cartilage and bone destruction, and systemic features,including cardiovascular, pulmonary, psychological, and skeletal disorders [2]. Possible risk factors for thedevelopment of RA include genetic background, smoking, silica inhalation and periodontal disease [1].A hyperplastic synovium is the major contributor to the cartilage damage in RA. The loss of the protectiveeffects of the synovium result in the alteration of the protein-binding characteristics of the cartilage surface,promoting synoviocytes (FLS) adhesion and invasion. These processes lead to the destruction of thesurface [2]. Bone erosion then follows rapidly (affecting 80% of patients within 1 year after diagnosis [1]).Cytokines present in the synovial fluid, particularly macrophage colony-stimulating factor (M-CSF) andreceptor activator of NF-kB ligand (RANKL), promote osteoclast differentiation and invasion of theperiosteal surface adjacent to articular cartilage [3]. Tumor Necrosis Factor alpha (TNF-α) and Interleukin(IL) -1, 6, and potentially 17 amplify osteoclast differentiation and activation.Studies in Europe have shown that there is a gradient in the prevalence of RA, starting from a lowprevalence in the South (e.g. Italy 0.31%) [4], to a higher prevalence in the North (e.g. Finland 0.8%) [5].While no formal epidemiológica! studies on RA have been carried out in Malta yet, a total ofapproximately 600 patients with the disease are followed up at the Rheumatology Clinic at St. Luke'sHospital, giving a prevalence of 0.16% [6].The use of different case definitions makes the estimates vary as widely as 25 to 115 per 100,000 [7]. Theannual incidence rate of RA recorded in studies varies between 20 and 50 cases per 100,000 in NorthernEuropean countries, but there are indications that it may be lower in Southern European countries [8,9].Studies of the incidence and prevalence of RA suggest variations between different populations even withinthe same country. Possible explanations include regional variation in behavioral factors, climate,environmental exposures, RA diagnosis, and genetic factors [7].Currently, treatment focuses on controlling symptoms and preventing further joint damage. Medicationsused in the trea ent of lude non-steroidal anti-inflammatory drug (NSAIDs), disease-modifyinganti-rheumatic drug (DMARDs), TNF-α inhibitors, IL-6 inhibitors, T-cell activation inhibitors, B-celldepletors, Janus kinase (JAK) inhibitors, and steroids [10] (Figure 1). Since all current treatments for RAare focusing on different areas of the immune system at the synovial compartment, a good understanding ofthe immunologic processes which occur throughout RA is vital for a better insight of the treatment66 CiteFavoritesSHARERESOURCES%Similar articlesCited by other arLinks to NCBI Da

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*Role of TNF(Tumor necrosis factor and cancer) in Rheumatoid arthritis:              *TNF inhibitors…