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Sci. Signal., 1 March 2011
Vol. 4, Issue 162, p. ra12
T Cells Lose Their Identity
Regulatory T cells (Tregs) inhibit the actions of inflammatory T cells during immune responses and prevent autoimmunity. Schenk et al. showed that adenosine triphosphate (ATP) signaling through purinergic receptors on Tregs inhibited their immunosuppressive effects and exacerbated tissue inflammation in mice. Worse still, autocrine ATP signaling made the Tregs lose their identity, through the loss of their signature transcription factor Foxp3, and induced their conversion into proinflammatory, interleukin-17–secreting cells. These data suggest that ATP signaling through purinergic receptors might be an effective therapeutic target to shape immune responses, a suggestion supported by the maintenance of the identity and immunosuppressive function of Tregs through pretreatment with a purinergic receptor antagonist.
Citation: U. Schenk, M. Frascoli, M. Proietti, R. Geffers, E. Traggiai, J. Buer, C. Ricordi, A. M. Westendorf, F. Grassi, ATP Inhibits the Generation and Function of Regulatory T Cells Through the Activation of Purinergic P2X Receptors. Sci. Signal.4, ra12 (2011).
Alterations in the adenosine metabolism and CD39/CD73 adenosinergic machinery cause loss of Treg cell function and autoimmunity in ADA-deficient SCID.
A. V. Sauer, I. Brigida, N. Carriglio, R. Jofra Hernandez, S. Scaramuzza, D. Clavenna, F. Sanvito, P. L. Poliani, N. Gagliani, F. Carlucci, et al. (2012)
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