CN-122005551-A - Method for enhancing regulatory B cell immunoregulation capacity and application thereof

Abstract

The application discloses application of mitochondrial acid 5 in preparing a product for enhancing the immunoregulation capacity of regulatory B cells, and provides a method for enhancing the immunoregulation capacity of the regulatory B cells, wherein the mitochondrial acid 5 is used for preprocessing the regulatory B cells, promoting the expression of interleukin-10 in the regulatory B cells and enhancing the treatment effect of the regulatory B cells on autoimmune diseases, chronic inflammatory diseases and/or organ transplant rejection, so the application also requests to protect the application of the mitochondrial acid 5 in preparing a synergist of a medicament for treating the autoimmune diseases, chronic inflammatory diseases and/or organ transplant rejection. The application develops a safe, efficient and specific method for promoting B lymphocyte differentiation to functional Bregs and secretion of interleukin-10, which can effectively inhibit overactive immune response and avoid self tissue injury.

Inventors

• PENG YANWEN
• LI YANLING
• ZHANG JUNJIE
• WU MENGYE
• HUANG YUYING

Assignees

• 中山大学附属第三医院

Dates

Publication Date

20260512

Application Date

20260318

Claims (10)

1. 1. Use of mitochondrial acid 5 for the preparation of a product for enhancing the immunomodulatory capacity of regulatory B cells.
2. 2. A product for enhancing the immunoregulatory capacity of regulatory B cells, characterized in that the product comprises mitochondrial acid 5 as an active ingredient.
3. 3. The product according to claim 2, characterized in that the concentration of mitochondrial acid 5 in the product is 5-100 μm.
4. 4. A product according to claim 3, characterized in that the concentration of mitochondrial acid 5 in the product is 50 μm.
5. 5. A method for enhancing the immunoregulatory capacity of regulatory B cells, characterized in that the product of any one of claims 2-4 is used in combination with regulatory B cells.
6. 6. Use of mitochondrial acid 5 for the manufacture of a potentiator of a medicament for the treatment of autoimmune diseases, chronic inflammatory diseases and/or organ transplant rejection.
7. 7. The use according to claim 6, wherein the autoimmune disease is multiple sclerosis, systemic lupus erythematosus and/or rheumatoid arthritis; the chronic inflammatory disease is inflammatory bowel disease.
8. 8. The use according to claim 7, wherein the inflammatory bowel disease is colitis.
9. 9. The use of claim 6, wherein the medicament is a regulatory B cell.
10. 10. A composition for treating autoimmune diseases, chronic inflammatory diseases and/or organ transplant rejection, characterized in that the composition comprises regulatory B cells pretreated with mitochondrial acid 5 as an active ingredient.

Description

Method for enhancing regulatory B cell immunoregulation capacity and application thereof Technical Field The application relates to the technical field of biological medicines, in particular to a method for enhancing the immunoregulation capacity of regulatory B cells and application thereof. Background Regulatory B cells (regulatory B cells, bregs) are a subset of B lymphocytes defined by function, mainly by secretion of the inhibitory cytokine interleukin-10 (interleukin-10, il-10) to regulate the immune response. Bregs numbers or dysfunctions are associated with a variety of pathological conditions including autoimmune diseases (e.g., multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis), chronic inflammatory diseases (e.g., inflammatory bowel disease), and organ transplant rejection. Thus, a therapeutic strategy that selectively induces functionality Bregs would be of great clinical value. Currently, some molecules have been reported to have the ability to induce Bregs, such as certain Toll-like receptor agonists, CD40 ligands, and the like. However, existing inducers generally have the defects of (1) low specificity, bregs induction and activation of other proinflammatory immune cells, 2) limited induction efficiency, and (3) in vivo application with large side effects or toxicity. Mitochondrial acid 5 (Mitochonic acid, MA-5), 4- (2, 4-difluorophenyl) -2- (1H-indol-3-yl) -4-oxobutanoic acid, is a compound derived from the plant growth hormone indole-3-acetic acid. MA-5 has the ability to modulate energy metabolism and reduce mitochondrial oxidative stress to improve mitochondrial function, and also up-regulate mitochondrial autophagy (mitophagy) to reduce mitochondrial apoptosis by targeting mitochondrial proteins (mitofilin). Therefore, the technology for enhancing Bregs immunoregulation is explored, the research and development of the medicine for treating diseases depending on Bregs immunoregulation is facilitated, and the novel inducer capable of safely, efficiently and specifically promoting B lymphocytes to differentiate into functional Bregs and secrete IL-10 is developed, so that the novel inducer has important scientific significance and clinical application value. Disclosure of Invention The invention aims to overcome the defects in the prior art and provide a method for enhancing the immunoregulation capacity of regulatory B cells and application thereof. A first object of the present invention is to provide the use of mitochondrial acid 5 for the preparation of a product for enhancing the immunomodulatory capacity of regulatory B cells. It is a second object of the present invention to provide a product that enhances the immunomodulatory capacity of regulatory B cells. It is a third object of the present invention to provide a method of enhancing the immunomodulatory capacity of regulatory B cells. A fourth object of the present invention is to provide the use of mitochondrial acid 5 in the manufacture of a potentiator of a medicament for the treatment of autoimmune diseases, chronic inflammatory diseases and/or organ transplant rejection. A fifth object of the present invention is to provide a composition for treating autoimmune diseases, chronic inflammatory diseases and/or organ transplant rejection. In order to achieve the above object, the present invention is realized by the following means: the present invention claims the use of mitochondrial acid 5 (MA-5) for the preparation of a product for enhancing the immunomodulatory capacity of regulatory B cells (Bregs). Preferably, the enhancing the immunoregulatory capacity of regulatory B cells is specifically promoting the expression of interleukin-10 (IL-10) of regulatory B cells. Regulatory B cells (Bregs) actively suppress excessive immune responses by secreting inhibitory cytokines (mainly IL-10), thereby maintaining immune tolerance and preventing autoimmune damage. Thus, the present invention also claims a product for enhancing the immunomodulatory capacity of regulatory B cells, said product having mitochondrial acid 5 as an active ingredient. Preferably, the concentration of the mitochondrial acid 5 in the product is 5-100 mu M. More preferably, the concentration of mitochondrial acid 5 in the product is 50 μm. The invention also claims a method for enhancing the immunoregulatory capacity of regulatory B cells, using any of the above products in combination with regulatory B cells. Preferably, when any of the above products is mixed with regulatory B cells, the concentration of regulatory B cells after mixing is 1X 10 6/mL and the concentration of mitochondrial acid 5 after mixing is 50. Mu.M. The invention also claims the use of mitochondrial acid 5 in the manufacture of a potentiator for a medicament for the treatment of autoimmune diseases, chronic inflammatory diseases and/or organ transplant rejection. Preferably, the autoimmune disease is multiple sclerosis, systemic lupus erythematosus and/or rheumatoid a