Role of the NF-kB family member RelB in regulation of Foxp3 + regulatory t cells in vivo

Junhui Li, Shuqiu Chen, Wenhao Chen, Qifa Ye, Yaling Dou, Yue Xiao, Lei Zhang, Laurie J. Minze, Xian C. Li, Xiang Xiao

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The NF-kB 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 2 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 2 / 2 Relb 2 / 2 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. The Journal of Immunology, 2018, 200: 1325–1334.

Original languageEnglish (US)
Pages (from-to)1325-1334
Number of pages10
JournalJournal of Immunology
Volume200
Issue number4
DOIs
StatePublished - Feb 15 2018

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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