Immunity . . . With new developments, The Dong Chen team at Tsinghua University revealed that transcription factor Tox2 can promote the development of T-cells by regulating chromatin accessibility.

Finaturet follicle helper cells (TFH) cells provide the necessary help for B cells in the germinal center (GC) reaction.BCL6 is an essential transcription factor in TFH cells.on November 12, 2019, Dong Chen team, Institute of immunology, Tsinghua University, published a research paper entitled "the transcription factor tox2 drives T follicular helper cell development via regulating chromatin accessibility" on immunity.this study revealed that BCL6 can regulate the differentiation and development of TFH by up regulating tox2 and tox, and tox2 can directly activate the chromatin accessibility of TFH related genes including BCL6.it provides a new idea and target for vaccine development and antibody mediated autoimmune disease treatment in the future.T follicular helper cell (TFH) is a special effector cell, CD4 + T cell subpopulation, which is required for the formation of germinal center (GC).phenotypically, TFH cells are isolated from the surface of chemokine receptor CXCR5, which contributes to the migration of TFH cells to B-cell follicles.transcription factor (TF) BCL6 is selectively expressed in TFH cells and is critical for TFH cell differentiation.the molecular mechanism of the basic function of BCL6 in TFH cells is not clear.BCL6 antagonizes the signal axis mediated by interleukin-7 receptor (IL-7R) and downstream TF STAT5, suggesting that it inhibits the activity of AP1 to limit BLIMP1 expression.there are some ways to promote the expression of BCL6 in TFH cells.cytokine environment is critical for TFH cell differentiation.IL-6 promotes the development of TFH cells by activating tfstat3 and inducing the expression of bcl-6 mRNA, and inhibits the signal transduction of type I interferon (IFN).IL-21 plays an important role in the differentiation of TFH cells and co stimulation of T helper cell differentiation. It plays a role at the level of T cell receptor signal bodies through Vav1 (a signal molecule that controls the auxiliary function of T cells).however, in vitro, neither IL-6 nor IL-21 was sufficient to induce the complete TFH procedure leading to the expression of BCL6 and CXCR5 proteins.IL-2 neutralization combined with exogenous IL-6 and IL-21 can reduce the inhibition of IL-6 and IL-21.the expression of BCL6 and the promotion of TFH may be achieved by activating STAT5 and inducing transcription regulator BLIMP1, which can inhibit the expression of BCL6. However, unlike other T helper (th) subtypes, the use of cytokine mixture can not effectively induce TFH cells in vitro, which suggests that other mechanisms are involved. here, the researchers studied the molecular pathway of inducing BCL6 gene expression and emphasized the BCL6 dependent function in the commitment process of TFH cells. integrated whole genome BCL6 occupation and differential gene expression analysis in TFH cells suggested that transcription factor tox2 played an important role in the differentiation of TFH cells. the ectopic expression of toxo2 is enough to drive the development of BCL6 expression and TFH. in the whole genome microarray-seq analysis, there were tox2 binding sites related to the differentiation and function of TFH cells, including BCL6. measured by atac-seq, tox2 binding was associated with increased chromatin accessibility at these sites. tox2 and / or mice showed that TFH differentiation was defective, and the inhibitory effect of toxic 2 and related transcription factor tox eliminated the differentiation of TFH. therefore, the tox2-bcl6 axis establishes a transcription feed-forward loop to promote TFH programs. original link: