It is revealed that E protein mediates the regulation of the effect of TCR signal on the differentiation of the effect Treg cells.

Regulatory T-cells (Treg) are T cells with immunosuppressive function, the main function of which is to suppress the effect of T-cell-mediated immune response and maintain the body's immune tolerance.
-effect Treg only accounts for a small part of secondary lymphatic organs and peripheral circulatory Treg cells, most of which are distributed in various tissue organs, the effect Treg is a group of Treg cells that have received antigen stimulation, relatively high degree of activity and have strong immunosuppressive function, these cells can quickly migrate into the site of the immune response, play the function of immunosuppression, prevent the immune response of T-cell-mediated too strong body damage.
has found that TCR signals are essential to the maintenance of the steady state and function of the active Treg cells, but the specific regulatory mechanism is not clear.
E protein is a very important transcription factor that regulates the development of thymus cells, which can be combined to the "E-box" region of the target gene, as a transcription activator or transcription inhibitor, and then regulate the transcription of the target gene. the activity of the
E protein is mainly regulated by the Id protein, which inhibits the function of the E protein.
previous studies have found that E proteins regulate the development of Treg cells (Ping Gao et.al, JEM, 2014, 211 (13): 2651-68), what is the effect of E proteins on treg cells that have matured? In addition, The TCR signal can reduce the activity of E protein, so is the E protein mediated the regulation of the effect Treg cell differentiation of the TCR signal? These problems have yet to be solved. On February 15,
, Zhang Fuping, a research team from the Institute of Microbiology of the Chinese Academy of Sciences, published the latest research results entitled E-protein regulatory network links TCR signaling to effector Treg cell in the Proceedings of the National Academy of Sciences (PNAS).
the work reveals that E protein mediates the regulation of The Effect Treg cell differentiation of TCR signals, and clarifies the molecular mechanism of E protein regulation effect Treg cell differentiation.
this study will greatly deepen people's understanding of the mechanism and regulatory process and regulatory mechanism of effect-based Treg cell differentiation and its immune regulation.
Zhang Fuping's team used E protein conditional knockout mice to specifically knock out E proteins in cells that expressed Foxp3, and found a significant increase in Treg cells in mice with E protein conditional knockout; Treg cells that are missing E proteins increase the expression of activation-related molecules - CD103, KLRG-1, ICOS, IRF4, etc., making Treg cells more effective Treg, making it easier to enter non-lymphatic tissues (e.g. lung, liver, intestinal inherent layers, etc.).
more likely to enter the inflammatory site to perform immunosuppressive function in pathological conditions such as experimental encephalomyelitis.
the study of the molecular mechanism of E protein regulation Treg cells, E protein can be directly combined to the gene regulatory region of the active Treg cell-related molecules (CD103, KLRG-1, ICOS, IRF4, etc.) and then regulate the expression of these molecules, thus affecting the activation state, migration and immunosuppressive function of Treg cells.
normal lying, E protein can be directly combined with the gene control region of the active Treg cell-related molecules, inhibit the expression of these genes, the absence of E protein can relieve this inhibition, promote Treg cell differentiation to Treg, tend to migrate to non-lymphatic tissue, show better immunosuppressive activity and better stability;
the project reveals that E protein as the target of TCR signal, directly mediates the regulation of the differentiation of the effect Treg cell, fills the gap of the "TCR signal-effect Treg cell" regulatory network, and the research will deepen people's understanding of the regulation of Treg cell stability and its immune regulation mechanism and regulatory process and regulatory mechanism.
Given the central role of regulatory T cells in maintaining autoimmune tolerance, the study will provide new opportunities for regulating T-cells to be used in many areas such as the treatment of cancer, autoimmune diseases, chronic infections, and transplant endurance. Han Xiaoxuan, Ph.D. of the
Institute of Microbiology, is the first author of the paper, and Zhang Fuping is the author of the paper.
the research is supported by the strategic leading science and technology project of the Chinese Academy of Sciences, the National Natural Science Foundation of China and the national science and technology major special projects.
Source: Institute of Microbiology.