Method for regulating and controlling activation of Treg cells

A cellular and regulatory technology used in the field of biomedicine

Pending Publication Date: 2021-05-18
INST OF MICROBIOLOGY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The function of MLL1 is not limited to stem cells. For example, the lack of MLL1 causes defects in the development and survival of B cells, but there are few related studies on T cells. Only literature studies have shown that MLL1 protein can bind to GATA3 and Th2 cells. Maintenance of memory Th2 cell immune responses at factor locus-specific loci

Method used

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  • Method for regulating and controlling activation of Treg cells
  • Method for regulating and controlling activation of Treg cells
  • Method for regulating and controlling activation of Treg cells

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Example 1 CD4-Cre-Mll1 fl / fl Construction of knockout mice

[0035] CD4-Cre-Mll1 was obtained by mating Mll1 fl / fl mice with CD4-cre transgenic mice fl / fl mice. where Mll1 fl / fl The construction method refers to the prior art. CD4-cre transgenic mice were purchased from Jackson Laboratory, number 022071.

Embodiment 2

[0036] Example 2 Effect of MLL1 on T cell development in mice

[0037] CD4-Cre-Mll1 fl / fl Mouse thymocytes were stained by flow cytometry, and it was found that the defect of MLL1 in T cells did not lead to defects in the development of thymic T cells and Treg cells ( figure 1 ).

Embodiment 3

[0038] Example 3 The effect of MLL1 on the activation of conventional T cells

[0039] CD4-Cre-Mll1 fl / fl For mice, spleen and lymph node single cell suspensions were prepared and analyzed by flow cytometry. The results showed that compared with WT mice, conventional CD4 cells CD44 hi CD62 lo The cell ratio did not change ( figure 2 A).

[0040] And detect the secretion level of IFN-γ in the body, the specific detection method is to take 2×10 6 The number of mouse lymphocytes was added to a 24-well cell culture plate with a final concentration of 10ng / mL PMA and 1uL inomycin, and 1uL Monensin was gently mixed, placed in an incubator for 3-4h, and then flow stained.

[0041] The results showed that compared with WT mice, the secretion of IFN-γ was not decreased and was not affected by MLL1 KO conventional CD4 T cells or CD8 T cells in splenic lymph nodes ( figure 2 B).

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Abstract

The invention belongs to the technical field of biological medicines, and discloses a method for regulating and controlling the activation of Treg cells. Research results show that MLL1 does not influence the normal development of thymus T cells; the deletion of the MLL1 does not affect the activation of conventional T cells and the secretion level of IFN-gamma, but the specific knockout of the MLL1 in the Treg cells affects the activation of the Treg cells, resulting in obvious immune activation in mice; afterwards, this is also observed in an experimental allergic encephalomyelitis model (EAE), MLL1KO mice cannot effectively limit the progress of the course of disease, and it is analyzed that the ratio of Treg in CNS cells is reduced, which suggests that the MLL1KO mice cannot effectively activate migration and inhibit the development of autoimmune diseases. The research finds that the molecular mechanism of the Treg cells playing an immunosuppressive effect is promoted to be further recognized, and a new treatment strategy is provided for anti-tumor immunity.

Description

technical field [0001] The invention relates to the technical field of biomedicine, and more specifically, relates to a method for regulating the activation of Treg cells. Background technique [0002] Regulatory T cells are a subset of CD4-positive T cells with immunosuppressive activity. Although the number of regulatory T cells is small, generally accounting for only about 10% of CD4-positive cells, they are important for maintaining the body's immune homeostasis and autoimmune resistance. Acceptance is crucial. Complete deficiency of regulatory T cells leads to fatal immune system dysregulation, causing IPEX (immunoregulation, polyendocrinopathy, enteropathy, and X-linked genetic disorder) syndrome. However, the excess of Treg can also impair beneficial immune responses, for example, the number of Treg cells in the local tumor tissue of cancer patients increases significantly, thereby inhibiting the body's anti-tumor immune response. Studies in recent years have shown ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/113C12N5/10A61K31/7088A61P35/00
CPCC12N15/1137C12N9/1007C12N5/0637A61K31/7088A61P35/00C12N2310/14C12N2320/30C12N2510/00
Inventor 周旭宇王婷张建华
Owner INST OF MICROBIOLOGY - CHINESE ACAD OF SCI
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