| First Author | Li J | Year | 2018 |
| Journal | J Immunol | Volume | 200 |
| Issue | 4 | Pages | 1325-1334 |
| PubMed ID | 29298831 | Mgi Jnum | J:257627 |
| Mgi Id | MGI:6116024 | Doi | 10.4049/jimmunol.1701310 |
| Citation | Li J, et al. (2018) Role of the NF-kappaB Family Member RelB in Regulation of Foxp3(+) Regulatory T Cells In Vivo. J Immunol 200(4):1325-1334 |
| abstractText | The NF-kappaB family member RelB is an important transcription factor that is capable of regulating diverse immune and inflammatory responses. However, its role in the regulation of Foxp3(+) regulatory T cells (Tregs) in vivo is poorly defined. In this study, we demonstrated that germline deletion of Relb resulted in systemic autoimmunity, which is associated with significant accumulation of Foxp3(+) Tregs in lymphoid and nonlymphoid organs. Foxp3(+) Tregs from RelB-deficient mice were functional and capable of suppressing T effector cells in vitro and in vivo, but Foxp3(-) T effector cells from RelB-deficient mice showed features of hyperactivation and spontaneously produced high levels of IL-2. Surprisingly, mice with conditional deletion of Relb in T cells (Cd4(Cre)Relb(f/f) mice) or specifically in Foxp3(+) Tregs (Foxp3(Cre)Relb(f/f) mice) did not show signs of autoimmunity and had similar frequencies of Foxp3(+) Tregs in the periphery as wild-type C57BL/6 controls. Both strains of conditional knockout mice also had a normal conventional T cell compartment. However, reconstituting Rag-1(-/-)Relb(-/-) hosts with wild-type C57BL/6 bone marrow cells led to hyperactivation of T effector cells, as well as marked expansion of Foxp3(+) T cells. These data suggest that the autoimmune phenotype in germline RelB-deficient mice is most likely caused by T cell-extrinsic mechanisms, and further studies are warranted to uncover such mechanisms. |
