Application of pcbp1 gene or its protein regulator in immune system diseases

A use and inhibitor technology, applied in allergic diseases, medical preparations containing active ingredients, anti-inflammatory agents, etc., can solve the problems of expensive, non-targeted pro-inflammatory cytokines, etc.

Active Publication Date: 2022-07-26
SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Targeting pro-inflammatory cytokines has also become an effective means and important direction for many autoimmune treatments, but there is no effective means of targeting pro-inflammatory cytokines except for monoclonal antibody drugs (which are expensive)

Method used

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  • Application of pcbp1 gene or its protein regulator in immune system diseases
  • Application of pcbp1 gene or its protein regulator in immune system diseases
  • Application of pcbp1 gene or its protein regulator in immune system diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0114] Example 1 Screening of autoimmune disease-related factors

[0115]Using a variety of mouse autoimmune models, it was found that GM-CSF produced in CD4+ T cells is the main pathogenic factor of autoimmune diseases, experimental autoimmune encephalomyelitis models (EAE), arthritis models such as CIA or SKG-arthritis model, interstitial lung disease (SKG-ILD) model in SKG mice, etc. Among the subtypes of CD4+ T cells, Th1, Th2, and Th17 can all secrete GM-CSF. Some studies believe that there is a type of CD4+ T cells that only secrete GM-CSF without simultaneously expressing IFNγ or IL17a, named ThGM .

[0116] Th1 cells are a CD4+ T cell subtype that mainly expresses IFNγ, and its secretion of GM-CSF has been proved to be necessary for the pathogenesis of EAE; Th17 cells are a CD4+ T cell subtype that mainly expresses IL17, which was first thought to cause inflammation by secreting IL17. and autoimmune diseases, and studies have found that knockout or antibody neutraliz...

Embodiment 2

[0118] Example 2 GM-CSF related gene screening

[0119] Post-transcriptional regulation plays an important role in the expression of GM-CSF, and the stability of GM-CSF mRNA determines the level of its expression. The regulation at the post-transcriptional level must rely on RNA-binding proteins to function. At least 1500 RNA-binding proteins have been found in the human genome, and the expression of many RNA-binding proteins is tissue- and spatiotemporally specific. Through the detection of high-throughput sequencing data (GSE48138), nearly 100 RNA-binding proteins were found to be highly expressed or have a dynamic trend in T lymphocytes, suggesting that they may have functions in T lymphocytes.

Embodiment 3

[0120] Example 3 Screening of lymphocyte-specific RNA binding proteins

[0121] 3.1 Construction of RNA-binding protein library

[0122] According to the results in Example 2, nearly 100 RNA-binding proteins related to lymphocyte development and differentiation were screened out, and an shRNA library was established, of which 80 RNA-binding proteins most closely related to the RNA-binding domain were shown in Table 1. , and designed shRNA for it, a total of about 300 shRNA.

[0123] Table 1: RNA-binding proteins for shRNA screening

[0124]

[0125] 3.2 RNA-binding protein knockdown screen

[0126] In view of the shortcomings of the primary effector T cells, which have a long differentiation time and cannot proliferate in large quantities, Jurkat cells (human peripheral blood leukemia T cells, purchased from the Cell Resource Center, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences) were selected to establish a screening model.

[0127] (1) Jurkat...

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Abstract

The invention provides the application of PCBP1 gene or its protein regulator in immune system diseases. Specifically, the present invention relates to the application of poly(C)-binding protein 1 (poly(C)-binding protein 1, PCBP1) modulators in immune system diseases; more specifically, poly(C)-binding protein 1 (poly(C) Use of ‑binding protein 1, PCBP1) inhibitors in autoimmune diseases.

Description

technical field [0001] The invention belongs to the field of biomedicine. Specifically, it relates to the application of poly(C)-binding protein 1 (poly(C)-binding protein 1, PCBP1) modulators in immune system diseases; more specifically, poly(C)-binding protein 1 (poly(C)-binding protein 1. Application of PCBP1) inhibitors in autoimmune diseases. Background technique [0002] Autoimmune disease is a type of disease in which the body's immune system mistakenly recognizes its own organs, tissues and cells, induces an immune response, and then causes self-injury. Its incidence is as high as 5%-8% in the whole population, and it is the third major disease after cardiovascular disease and tumor. About 100 autoimmune diseases have been diagnosed so far. Common autoimmune diseases are: multiple sclerosis (MS), rheumatoid arthritis (RA), autoimmune myocarditis, systemic lupus erythematosus (SLE), type I Diabetes, autoimmune thyroiditis, psoriasis, etc. Taking multiple sclerosis...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61P29/00A61P37/02
CPCA61K45/00A61P29/00A61P37/02
Inventor 常兴王志章
Owner SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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