TNFα: Activator or inhibitor of regulatory T cells?

TNF alpha is a cytokine that is central to the pathogenesis of several autoimmune diseases. More specifically, the deleterious effects of TNF alpha in rheumatoid arthritis (RA) are well established. The proinflammatory influence of TNF alpha in RA is related both to direct effects mediated by the induction of other proinflammatory cytokines, metalloproteinases, and free radicals; and to modulation of the regulatory T cells (Tregs). Furthermore, the TNF alpha antagonists used to treat RA can induce the emergence of a distinctive Treg subpopulation. Nevertheless, a recent body of data suggests that TNF alpha may also exert anti-inflammatory effects, which may be mediated in part via Tregs. TNF alpha binds to the TNF receptor 2 expressed preferentially at the Treg surface, thereby activating and promoting the development of Tregs. Data from patients with RA and more recent evidence obtained in the absence of disease are consistent with a paradoxical effect of TNF alpha on Tregs. TNF alpha may have different effects on naturally occurring Tregs and induced Tregs. (C) 2011 Published by Elsevier Masson SAS on behalf of the Societe Francaise de Rhumatologie.