Nat Immunol TCF-1 controls the function of Treg cells in inflammation, CD8 T cell toxicity and rectal cancer

There is a cell in our body that is responsible for monitoring, checking other cells in the body, and removing abnormal cells (cancerous or infected by pathogens)-immune cells
.

Immune cells can be roughly divided into innate immune cells and adaptive immune cells, which can initiate non-specific and specific immune responses against antigens, respectively
.

There are two main types of adaptive immune cells.
B cells mainly rely on the secretion of specific antibodies to achieve extracellular neutralization of antigens; T cells mainly include CD8 and CD4 T cells, and CD8 T cells are mainly responsible for the killer task.
Pathogen infection or cancer) to eliminate; and CD4 T cells (also called T helper cells, T helper cells) play a role in assisting other immune cell response and differentiation regulation
.

CD4 T cells can differentiate into different subgroups, one of which is found to play an important role in the inflammatory response, called T helper 17 Cells (Th17)
.

Regulatory T cells (Treg) are a special subset of CD4 T cells that specifically express the transcription factor FOXP3
.

One of the main functions of regulatory T cells is to suppress excessive immune responses from other immune cells [1]
.

In recent years, more and more evidences have shown that Treg is a cell type that includes multiple subpopulations.
Each subpopulation has different expression of transcription factors, making it similar to other CD4 T cell subpopulations.
These transcriptions Factors include RORγT, GATA3 and TBET [2,3]
.

In previous work, the Khashayarsha Khazaie team at the University of Chicago found that in human colorectal cancer (CRC) and mouse intestinal polyposis (polyposis) disease models, they found that because of the high expression of β-catenin, regulatory T cells can differentiate in a pro-inflammatory direction.
This leads to worsening of the disease [4,5]
.

In T cells, β-catenin has an important DNA binding cofactor, T cell transcription factor 1 (transcription factor T cell factor 1, TCF-1) [6]
.

Previous studies have shown that the loss of TCF-1 can lead to an increase in thymus regulatory T cells [7], therefore, TCF-1 may have an important function in regulatory T cells
.

In order to determine the function of TCF-1 in Treg, on August 12, 2021, the Khashayarsha Khazaie team (co-one as Abu Osman and Bingyu Yan) published an article TCF-1 controls Treg cell functions that regulate inflammation, CD8+ T in Nature Immunology.
cell cytotoxicity and severity of colon cancer
.

The researchers constructed a specific knockout mouse model of TCF-1 in Treg cells, and performed single-cell transcriptome analysis of Treg cells in mesenteric lymph nodes (MLN)
.

According to the expression level of specific transcription factors (such as Mif, Maf, Ikzf2), the subgroup composition of MLN Treg cells was determined, and it was found that the lack of TCF-1 did not affect the main function of Treg cells---immunosuppressive effect.
However, Most Treg cell subgroups have acquired the pro-inflammatory and intestinal localization properties very similar to Th-17 cells to varying degrees
.

So, what effect will these Treg cells lacking TCF-1 have on the immune environment of the intestine? By comparing intestinal polyp model mice with missing TCF-1 Treg cells and control intestinal polyp model mice with normal TCF-1 expressing Treg cells, the researchers found that in the rectum and small intestine, there are missing TCF-1 Treg cells Intestinal polyp model mice, the number and severity of polyps/tumors increased significantly
.

More importantly, the researchers found that the expression of TCF-1 in the Treg cells in the tissues of patients with rectal cancer [8] was significantly lower than that in the normal tissues adjacent to the cancer and the Treg cells in the peripheral blood (PBMC) of these patients, and The Treg cells in these tumor tissues also showed differentiation to pro-inflammatory directions similar to Th17 cells
.

It can be seen that, as summarized in the figure below, TCF-1 plays an important role in the function regulation of Treg cells
.

TCF-1 can regulate whether Treg cells differentiate in the direction of pro-inflammatory, which in turn determines the severity of rectal cancer
.

Original link: https://doi.
org/10.
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The author has all legal rights, and offenders must be investigated.
Reprinting instructions [Non-original articles] The copyright of this article belongs to the author of the article.
Personal forwarding and sharing are welcome.
Reprinting is prohibited without permission.
The author has all legal rights, and offenders must be investigated. .