Chromatin remodeling complex in Treg function.
Regulatory T cells (Treg), formerly known as suppressor T cells, are essential for maintaining self-tolerance as well as immune homeostasis. Lack of Treg or normal function of Treg often leads to lymphoproliferative syndrome and autoimmunity in human and mouse. The chromatin remodeling BAF complex regulates gene expression through the activity of Brg. Genetic ablation of Brg gene in mouse resulted in early embryonic lethality. T cell failed to develop in the thymus when Brg is deleted at DN stage. Using a Brg conditional KO mouse model, we deleted Brg at the DP stage in the thymus. Unexpectedly, T cells developed and matured normally. However, these mice displayed lympho-proliferative syndrome 2-4 months of age with enlarged peripheral lymphoid organs and leukocyte infiltration in non-lymphoid organs. T cells from these mice turned into effector cells producing increased amounts of effector cytokines as early as 4 weeks after birth. Further analysis revealed that the Treg population was specifically affected by Brg deletion. In this mini-review, we will discuss in detail the properties of Tregs controlled by Brg and the potential underlying mechanisms for an unanticipated, specific role of the Brg-containing BAF complex in controlling Treg functions.
Jani
Anant
A
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Chi
Tian
T
Wan
Yisong Y
YY
D000818:Animals; D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017634:Self Tolerance; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D009687:Nuclear Proteins; C499503:Smarca2 protein, mouse; D014157:Transcription Factors; C513194:Smarca4 protein, mouse; D004265:DNA Helicases