Abstract
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.
Highlights
IntroductionFoxp[3] is the key transcription factor for Treg-cell differentiation and function; molecular mechanisms for its negative regulation are poorly understood
Regulatory T (Treg) cells are essential for maintenance of immune homeostasis
The role of YY1 in Treg-cell differentiation was of particular interest because YY1 expression was selectively low in induced Treg cells compared with in vitro-differentiated conventional T (Tconv) cells (Fig. 1a,b)
Summary
Foxp[3] is the key transcription factor for Treg-cell differentiation and function; molecular mechanisms for its negative regulation are poorly understood. YY1 inhibits differentiation and function of Treg cells by blocking Foxp[3]. Foxp[3] is involved in the control of differentiation and function of Treg cells. Deficiency of Foxp[3] expression in Treg cells causes both defective function of Treg cells and the acquisition of Tconv-cell properties[5,6,7]. Understanding the positive and negative regulation of Foxp[3] is critically important in controlling Treg cell-regulated immune responses, including those involved in autoimmune diseases, allergies, organ transplantation and cancer[7]. Other transcription factors including Foxo[1], Foxo[3], Runx[1], Runx[3], RXR/RAR and Notch[1] were shown to be involved in the induction of Foxp[3] expression[3,11,13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
