Soo Seok Hwang1,2,3, Sung Woong Jang1, Min Kyung Kim1, Lark Kyun Kim2,3, Bong-Sung Kim4,5,6, Hyeong Su Kim1, Kiwan Kim1, Wonyong Lee1, Richard A. Flavell2,3 & Gap Ryol Lee1
1 Department of Life Science, Sogang University, 35 Baekbeom-ro, Seoul 121-742, Korea. 2 Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. 3 Howard Hughes Medical Institute, Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut 06520, USA. 4 Department of Rheumatology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. 5 Department of Plastic and Reconstructive Surgery, Hand Surgery.Burn Center, Medical Faculty, RWTH Aachen University, Templergraben 55, 52062 Aachen, Germany. 6 Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Templergraben 55, 52062 Aachen, Germany.
Correspondence to : Gap Ryol Lee
Regulatory T (Treg) cells are essential for maintenance of immune homeostasis. Foxp3 is the key transcription factor for Treg-cell differentiation and function; however, molecular mechanisms for its negative regulation are poorly understood. Here we show that YY1 expression is lower in Treg cells than Tconv cells, and its overexpression causes a marked reduction of Foxp3 expression and abrogation of suppressive function of Treg cells. YY1 is increased in Treg cells under inflammatory conditions with concomitant decrease of suppressor activity in dextran sulfate-induced colitis model. YY1 inhibits Smad3/4 binding to and chromatin remodelling of the Foxp3 locus. In addition, YY1 interrupts Foxp3-dependent target gene expression by physically interacting with Foxp3 and by directly binding to the Foxp3 target genes. Thus, YY1 inhibits differentiation and function of Treg cells by blocking Foxp3.