T cells out of control-impaired immune regulation in the inflamed joint

Since their discovery over 15 years ago, intensive research has focused on the presence, phenotype and function of FOXP3+ regulatory T cells (Treg) in autoimmune disease. The questions whether Treg deficiencies underlie autoimmune pathology and whether or how Treg-related therapeutic approaches might be successful are still subject of a vivid debate. Very recently however, the topic of Treg extrinsic factors as the cause of regulatory defects in chronic autoimmune inflammation has become more prominent in the discussion. It is now clear that at the site of inflammation antigen presenting cells (APC) and pro-inflammatory cytokines drive effector T cells (Teff) skewing and plasticity and that Teff can become unresponsive to regulation. In addition, Treg expansion and function is affected by the inflammatory environment and data suggest that in certain conditions Treg may promote inflammation. This review summarizes the latest findings on changes in Teff homeostasis in autoimmune disease and focuses on how regulatory mechanisms that normally keep Teff under control are affected in the inflamed joints of arthritis patients. These findings have important clinical implications and will impact the development of new therapeutic strategies for autoimmune arthritis.


T cells out of control-impaired immune regulation in the inflamed joint.

Wehrens EJ, Prakken BJ, van Wijk F.

Nat Rev Rheumatol. 2012 Sep 18