Volume 27, Issue 1, Pages 5-7 (January 2018) Apoptotic Regulatory T Cells Retain Suppressive Function through Adenosine  Ulf H. Beier  Cell Metabolism  Volume 27, Issue 1, Pages 5-7 (January 2018) DOI: 10.1016/j.cmet.2017.12.013 Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 1 Apoptotic Tregs Can Suppress Effector T Cells through Adenosine (A–G) Model demonstrating how apoptotic Tregs suppress immune responses through adenosine. (A) Effector T cells (Teff) have an adequate antioxidant response countering reactive oxygen species (ROS). (B) Tregs have less NRF2 signaling and (C) are susceptible to ROS-induced damage (either ambient ROS, which is enriched in the TME, or internally produced ROS). ROS damage can lead to disruption of lipid bilayer membranes and cell death. (D) ATP released by the apoptotic Tregs is (E) dephosphorylated by CD39 and CD73 to adenosine (ADO, lower insert). (F) ADO can inhibit local Teff through the adenosine A2A receptor (A2AR, upper insert), which activates intracellular adenylate cyclase (AC), producing cyclic AMP (cAMP), which then activates protein kinase A (PKA). (G) PKA inhibits T cell receptor (TCR) signaling. NRF2, nuclear factor (erythroid-derived 2)-like 2; Keap1, Kelch like-ECH-associated protein 1. Cell Metabolism 2018 27, 5-7DOI: (10.1016/j.cmet.2017.12.013) Copyright © 2017 Elsevier Inc. Terms and Conditions