title: T cells out of control--impaired immune regulation in the inflamed joint.
abstract: Since the discovery of FOXP3+ regulatory T (T(REG)) cells over 15 years ago, intensive research has focused on their presence, phenotype and function in autoimmune disease. Whether deficiencies in T(REG) cells underlie autoimmune pathology and whether, or how, therapeutic approaches based on these cells might be successful is still the subject of debate. The potential role of T(REG)-cell extrinsic factors, such as proinflammatory cytokines and resistance of effector T cells to suppression, as the cause of regulatory defects in chronic autoimmune inflammation is an intensive area of research. It is now clear that, at the site of inflammation, antigen presenting cells (APCs) and proinflammatory cytokines drive effector T cell skewing and plasticity, and that these T cells can become unresponsive to regulation. In addition, expansion and function of T(REG) cells is affected by the inflammatory environment; indeed, new data suggest that, in certain conditions, T(REG) cells promote inflammation. This Review summarizes the latest findings on changes in effector T cell homeostasis in autoimmune disease and focuses on how mechanisms that normally regulate these cells are affected in the inflamed joints of patients with arthritis. These findings have important clinical implications and will affect the development of new therapeutic strategies for autoimmune arthritis.
authors: Center for Molecular and Cellular Intervention, Department of Paediatric Immunology, University Medical Centre Utrecht, P.O., AB Utrecht, The Netherlands.
authors: Ellen J
authors: EJ
authors: Wehrens
authors: Berent J
authors: BJ
authors: Prakken
authors: Femke
authors: F
authors: van Wijk
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D001168:Arthritis / Q000276:immunology / Q000473:pathology*; D015551:Autoimmunity / Q000276:immunology; D004195:Disease Models, Animal; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D007596:Joints / Q000276:immunology / Q000473:pathology*; D051379:Mice; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology*
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