| First Author | Schuster M | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 3 | Pages | 920-930 |
| PubMed ID | 28652399 | Mgi Jnum | J:251505 |
| Mgi Id | MGI:6100550 | Doi | 10.4049/jimmunol.1600877 |
| Citation | Schuster M, et al. (2017) c-REL and IkappaBNS Govern Common and Independent Steps of Regulatory T Cell Development from Novel CD122-Expressing Pre-Precursors. J Immunol 199(3):920-930 |
| abstractText | Foxp3-expressing regulatory T cells (Tregs) are essential regulators of immune homeostasis and, thus, are prime targets for therapeutic interventions of diseases such as cancer and autoimmunity. c-REL and IkappaBNS are important regulators of Foxp3 induction in Treg precursors upon gamma-chain cytokine stimulation. In c-REL/IkappaBNS double-deficient mice, Treg numbers were dramatically reduced, indicating that together, c-REL and IkappaBNS are pivotal for Treg development. However, despite the highly reduced Treg compartment, double-deficient mice did not develop autoimmunity even when aged to more than 1 y, suggesting that c-REL and IkappaBNS are required for T cell effector function as well. Analyzing Treg development in more detail, we identified a CD122(+) subset within the CD25(-)Foxp3(-) precursor population, which gave rise to classical CD25(+)Foxp3(-) Treg precursors. Importantly, c-REL, but not IkappaBNS, controlled the generation of classical CD25(+)Foxp3(-) precursors via direct binding to the Cd25 locus. Thus, we propose that CD4(+)GITR(+)CD122(+)CD25(-)Foxp3(-) cells represent a Treg pre-precursor population, whose transition into Treg precursors is mediated via c-REL. |
