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.

Immune mechanisms in inflammatory and degenerative eye disease

“…lost as a consequence of inflammation. This may be due in part to presence of inflammatory mediators in the eye, which can impede Treg induction and function, as well as to depletion from the eye of anti-inflammatory and Treg-inducing factors such as TGF-β and retinoic acid from through the compromised blood retinal barrier [32, 33]. These findings could help to explain how autoimmune uveitis can occur in the face of immune privilege.…”

IL-1R1 is expressed on both Helios+ and Helios−FoxP3+CD4+ T cells in the rheumatic joint

“…T reg prevalence and functionality in different settings of autoimmune disease has been studied extensively, both for understanding whether T reg deficiency is part of the disease aetiology and for setting a basis for T reg -mediated therapeutic approaches [2].…”

Regulation of Arthritis Severity by the Acid Sphingomyelinase

“…Regulatory T (T reg ) cells have also been reported to be involved in the pathogenesis of autoimmune diseases, including RA [39-42]. Previously, Asm-deficiency or Asm-inhibition has been linked to increased T reg frequencies in naïve mice [43, 44].…”