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Method for regulating and controlling body immunoreaction through regulation of skin DCs (dendritic cells)/ LCs (Epidermal Langerhans cells) by electric signal to be presented to T cell, and purpose of method

A technology for electrical signal regulation and body immunity, applied in the field of immunity, can solve the problems that antigen adsorption is easily affected by physical and chemical properties, the mechanism of action has not been clarified, and the effect of adjuvant immunity varies greatly, so as to enhance antigen absorption and biological immunity. Utilization rate, improved vaccine safety, low cost effect of electric field stimulation

Pending Publication Date: 2020-05-19
宋冰 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] Aluminum salt adjuvant: Aluminum salt adjuvant is the most successful and important adjuvant used in human vaccines so far, but there are still shortcomings: it cannot be freeze-dried; antigen adsorption is easily affected by physical and chemical properties, and often occurs in different batches. The immune effect of secondary adjuvants varies greatly, and the quality is unstable; erythema, swelling and induration appear at the injection site; aluminum salts are easy to accumulate in the body, especially in the brain
[0016] AS series adjuvants: AS series adjuvants can cause pain at the injection site, local inflammatory response, and induce inflammatory arthritis, and are prone to uneven mixing with antigens, and the production cost is relatively high
[0017] NB001 nano-adjuvant: This adjuvant can promote the immune enhancement of the body, but its mechanism of action has not yet been elucidated, and there is also the possibility of inducing adverse reactions such as autoimmune diseases and inflammation
[0018] Immunomodulators have been of great value in the prevention and treatment of diseases, but it has been found through clinical application that the currently widely used immunomodulators still inevitably cause some side effects, such as pain at the injection site, erythema and local rash; a small number of patients with intravenous administration Infusion reactions such as headache, fever, and elevated blood pressure may occur; after the use of immunosuppressants such as glucocorticoids, the body is prone to infection due to the suppression of immune function; when the use of immunomodulators artificially interferes with the body's immune response, it is easy to cause immunity. The function is disturbed again and induces new immune-related diseases; in addition, some immunosuppressants can also cause systemic edema, thrombocytopenia, congestive heart failure, low renal function, central nervous system poisoning symptoms, etc.
[0019] In addition, most of the immunomodulators currently in clinical use are expensive, especially imported preparations.
However, patients often need to use immunomodulators for a long time to treat diseases, which is expensive and burdens families and society.

Method used

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  • Method for regulating and controlling body immunoreaction through regulation of skin DCs (dendritic cells)/ LCs (Epidermal Langerhans cells) by electric signal to be presented to T cell, and purpose of method
  • Method for regulating and controlling body immunoreaction through regulation of skin DCs (dendritic cells)/ LCs (Epidermal Langerhans cells) by electric signal to be presented to T cell, and purpose of method
  • Method for regulating and controlling body immunoreaction through regulation of skin DCs (dendritic cells)/ LCs (Epidermal Langerhans cells) by electric signal to be presented to T cell, and purpose of method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] Example 1 In vitro cell powering experiment

[0059] Since it is difficult to isolate and maintain a sensitive homogeneous population of human DCs, several cell lines have been established to facilitate the study of DCs, one of which was used in this example: KG-1 cells (a cytokine-responsive CD34+ myelomonocytic cell line).

[0060] (1) Reagents and consumables required for in vitro cell powering:

[0061] ① Conductive solution Steinberg's solution preparation: dH2O 500ml, NaCl 3.4g, KCl0.05g, Ca(NO3).4H2O 0.08g, MgSO4.7H2O 0.205g, Trisasorb of buffer 0.56g, mix and dissolve according to the above ratio, add HCl to adjust the pH to 7.4

[0062] ②Preparation of conductive glass salt bridge: Heating and bending the glass tube of Zhongtong to make the shape required for power-on

[0063] ③Conductive electrode: put Ag wire or AgCl wire into Steinberg’s solution conductive liquid

[0064] ④ Preparation of agar conductive salt bridge gel: 100ml Steinberg’s solution, 2g A...

Embodiment 2

[0076] Example 2 Mice in vivo electrification experiment one

[0077] Based on the research results of in vitro cell electrification experiments, we believe that local electrical stimulation of mouse skin can eliminate some interfering factors in the in vitro experiments and provide a clear answer for the effect of EFs. At the same time, transgenic mice are of great significance for supporting and verifying hypotheses, so further confirmation of IL-18 and IL-18R gene knockout mice will significantly improve the reliability of this study.

[0078] (1) Selection of research objects: C57BL / 6 mice (wild type, WT), gene knockout IL-18 KO and IL-18RKO mice

[0079] (2) Consumables required for in vivo power-on of mice:

[0080] ① Skin conductive electrode patch: The skin conductive electrode patch selects medical conductive materials that can directly contact the skin, such as a disposable button-type ECG electrode patch, and trims it according to the electrified part so that the e...

Embodiment 3

[0098] Example 3 Mice in vivo electrification experiment two

[0099] In order to more intuitively detect the effect of EFs on the migration of LCs in the epidermis, we applied electricity to the ear skin of mice, and used fluorescent labeling to display the distribution and quantity of LCs in the ear epidermis, and analyzed the changes of LCs before and after electrification.

[0100] (1) Selection of research objects: C57BL / 6 mice (wild type, WT), gene knockout IL-18 KO and IL-18RKO mice

[0101] (2) Consumables required for in vivo power-on of mice:

[0102] ①Ear skin conductive electrode patches: also select medical conductive materials that can directly contact the skin, such as disposable button-type ECG electrode patches, and trim them to an appropriate size according to the mouse's ears, and weld the positive and negative electrodes. Placed on the ear of the mouse with an ear clip structure

[0103] ② Preparation of power supply device: specific DC or AC power genera...

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Abstract

The invention discloses a method for regulating and controlling body immunoreaction through the regulation of skin DCs (dendritic cells) / LCs (Epidermal Langerhans cells) by an electric signal to be presented to a T cell. The method comprises the following steps of: cells or skin tissues are put between an electrode A and an electrode B; a direct current power supply is connected between the electrode A and the electrode B; an electric field is formed between the electrode A and the electrode B; current enough to guide and control DCs / LCs cell migration and localization is given; and therefore, the skin DCs / LCs can be regulated through the electric signal to be presented to the T cell to regulate and control the body immunoreaction. The method disclosed by the invention has potential tobe used for preparing a novel vaccine adjuvant, or the method disclosed by the invention and other adjuvants are jointly used for regulating immunoreaction. The method can be used for targeting specific immunomodulators and accurate cancer treatment under a situation that the method is not induced and distributed by a chemical tendency, and common clinical side effects are reduced. Compared with existing common immunomodulators, the method disclosed by the invention has the advantages of a wide adjustable range and low cost, and is favorable for lightening the economic burdens of patients andthe society, and an operation condition of the method can be easily optimized.

Description

technical field [0001] The invention belongs to the technical field of immunity, and in particular relates to a method for regulating the body's immune response by regulating the presentation of skin DCs / LCs to T cells by electrical signals and its application. Background technique [0002] Various physical, chemical and biological factors in the environment can affect skin immunity. Dendritic cells (DCs) are professional antigen-presenting cells that can initiate adaptive immune responses to foreign antigens and maintain T cell tolerance to themselves. The skin and lymphoid organs are the first entry point for microbial pathogens and the initial site of the adaptive immune response, where DCs are most enriched. [0003] Skin DCs include epidermal Langerhans cells (LCs) in the epidermis and dermal DCs (DDCs) in the dermis. Both LCs and DDCs are capable of capturing foreign and self-antigens in vivo and presenting them to naive T cells. ( Tcell). Unlike other antigen-pre...

Claims

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Application Information

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IPC IPC(8): C12N13/00A61K39/39A61P35/00A61P37/02
CPCC12N13/00A61K39/39A61P37/02A61P35/00A61K2039/572A61K2039/55588A61K2039/585
Inventor 宋冰高兴华陈洪铎魏晓清高雅丽齐瑞群
Owner 宋冰
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