Driving Rel-iant Tregs toward an Identity Crisis Amy Li, Tyler Jacks  Immunity  Volume 47, Issue 3, Pages 391-393 (September 2017) DOI: 10.1016/j.immuni.2017.08.014 Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 1 p65 and c-Rel Have Partially Redundant Roles in Maintaining Treg Cell Identity and Function and Can Be Differentially Targeted Cell-intrinsic canonical NF-κB signaling through both p65 and c-Rel regulates the Treg cell transcriptional program (top, left). Abrogation of signaling in Treg cells due to loss of both subunits results in severe alteration of the Treg cell phenotype and drastic reduction in Treg cell numbers, resulting in severe autoimmunity and early death (top, right). Many Treg cell signature genes are downregulated, while there is increased expression of conventional CD4+ (Tconv) cell-associated genes like IFN-γ and interleukin-17 (IL-17). p65 is dispensable for tumor immune suppression, but required for preventing systemic inflammation (bottom, left). c-Rel loss in Treg cells results in only mild autoimmunity, but enhances anti-tumor CD8+ T cell responses, impairing the growth of transplanted tumor cells (bottom, right). Administration of pentoxifylline (PTXF) selectively depletes c-Rel in Treg cells, recapitulating the anti-tumor effect of Treg cell-specific c-Rel deletion. Immunity 2017 47, 391-393DOI: (10.1016/j.immuni.2017.08.014) Copyright © 2017 Elsevier Inc. Terms and Conditions