Science Sub-Journal: Xiamen University's Liu Wenxian team reveals a new mechanism that regulates the migration of mature T cells from the thymus to the periphery

Whether it is the current hot new tumor immunotherapy strategies represented by CAR-T and PD-1 antibody therapy , or the direct clearance of virus by T cells after the new coronavirus infection or the secretion of neutralizing antibodies by B cells, it has revealed that T cell subtypes The population is a key cell subpopulation for clearing tumors and fighting viral infections, which also means that the normal number and function of T cells are essential for maintaining the body's normal immune state
.

Whether it is the current hot new tumor immunotherapy strategy represented by CAR-T CAR-T and PD-1 antibody therapy , or after the new coronavirus infection , the immune infection T cells directly clear the virus or help B cells secrete neutralizing antibodies.
It is revealed that T cell subgroups are the key cell subgroups for clearing tumors and fighting viral infections, which also means that the normal number and function of T cells are essential for maintaining a normal immune state of the body
.

T cells develop from the thymus.
After undergoing a series of " checkpoints " screening in the thymus, such as beta selection, positive selection, and negative selection , only 2%-5% of thymic T cells mature and migrate from the thymus to the periphery.
Immune organs .
It is worth mentioning that in the late stage of negative selection, before entering the mature state and preparing to emigrate , thymic T cells have undergone a physiological process in which the TCR signal ( CD69 ) decreases and the migration signal ( S1P1 ) rises.
This precise physiological process regulates Mature thymus T cells migrate to the periphery .
However, little is known about what signaling mechanism regulates this process .

T cells develop from the thymus.

After undergoing a series of " checkpoints " screening in the thymus, such as beta selection, positive selection, and negative selection , only 2%-5% of thymic T cells mature and migrate from the thymus to the periphery.
Immune organs .
It is worth mentioning that in the late stage of negative selection, before entering the mature state and preparing to emigrate , thymic T cells have undergone a physiological process in which the TCR signal ( CD69 ) decreases and the migration signal ( S1P1 ) rises.

Recently, Xiamen University School of Life Sciences / Cell Biology, State Key Laboratory of Stress Research Group, Professor Liu Wenxian inScience Advancespublished in the journal entitled: Glycogen synthase kinase 3 Drives thymocyte Egress by Suppressing beta-catenin Activation of Aktresearch papers

This study reveals the important functions and regulatory mechanisms of the GSK3/β-catenin signaling pathway in regulating the migration of thymic mature T cells from the thymus, and provides a new molecular mechanism analysis for the signal regulation of T cell development and migration
.

This study reveals the important functions and regulatory mechanisms of the GSK3/β-catenin signaling pathway in regulating the migration of thymic mature T cells from the thymus, and provides a new molecular mechanism analysis for the signal regulation of T cell development and migration
.

The Wnt/β-catenin signaling pathway is known to play an important role in maintaining the characteristics of stem cells and cell differentiation.

Abnormal activation of this signal can promote the formation of tumors such as malignant cell proliferation

The Wnt/β-catenin signaling pathway is known to play an important role in maintaining the characteristics of stem cells and cell differentiation.
Abnormal activation of this signal can promote the formation of tumors such as malignant cell proliferation

The research team used GSK3afl/fl , GSK3bfl/fl ; CD4Cre ( DKO ) mouse analysis and found that T cells in the peripheral immune organs of DKO mice almost disappeared.
Using thymocyte tracing technology, they found that the migration of mature T cells in the thymus of DKO mice appeared.
Obvious flaws .
Through transcriptomics binding protein level analysis, it was found that the Foxo1/KLF2/S1P1 signaling pathway in DKO mouse thymic T cells was obviously defective.

The research team next explored how GSK3 regulates Akt kinase activity, and found that the high expression of β-catenin in the cytoplasm can directly promote Akt kinase activation.
The researchers found that the β-catenin in the cytoplasm mainly reduces Akt and its elimination.
The interaction of phosphatase PHLPP2 and PP2A inhibits the dephosphorylation of Akt by PHLPP2 and PP2A , thereby promoting Akt kinase activity .
In summary, this study is the first report GSK3 in the regulation of the thymus mature T an important role in cell moved out, and revealed for the first time in the immune cells of β-catenin does not rely on classical transcriptional regulation in the cytoplasm directly activated Akt new regulatory mechanisms .

The above work not only enriches and perfects the regulation mechanism of thymic mature T cell emigration, but also directly promotes the mechanism of Akt activity by cytoplasmic β-catenin .

It also provides resistance to a variety of tumors including leukemia and lymphoma in malignant proliferation and recurrence.
Provide new theoretical references in the exploration of other mechanisms .

The above work not only enriches and perfects the regulation mechanism of thymic mature T cell emigration, but also directly promotes the mechanism of Akt activity by cytoplasmic β-catenin .
It also provides resistance to a variety of tumors including leukemia and lymphoma in malignant proliferation and recurrence.

Professors Liu Wenxian and Professor Xiao Changchun from the School of Life Sciences of Xiamen University and Professor Fu Guo from the School of Medicine are the co-corresponding authors of this article.

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