Application of LYG1 in preparation of medicine for promoting immune reconstruction after hematopoietic stem cell transplantation

Abstract

The invention discloses application of a cytokine LYG1 in preparation of a medicine for promoting immune reconstruction after hematopoietic stem cell transplantation. The invention further discloses a medicine for promoting immune reconstitution after hematopoietic stem cell transplantation. The medicinal ingredient of the medicine is the cytokine LYG1. A large number of tests prove that the LYG1 deficiency can obviously inhibit immune reconstruction after hematopoietic stem cell transplantation, and the influence of the LYG1 deficiency of a recipient on the immune reconstruction after hematopoietic stem cell transplantation is more obvious. Therefore, the LYG1 treatment is given to a transplantation recipient, namely a patient, so that the immune reconstitution of the patient can be accelerated.

Description

Technical Field

[0001] This invention relates to the field of biotechnology, and in particular to the application of the cytokine LYG1 in the preparation of drugs for promoting immune reconstitution after hematopoietic stem cell transplantation. Background Technology

[0002] Hematopoietic stem cell transplantation (alto-HSCT) is one of the most effective treatments for hematological malignancies. Poor immune reconstitution and weakened immune function after transplantation are key factors affecting clinical prognosis, especially with the widespread adoption of haploidentical hematopoietic stem cell transplantation in recent years, infection and relapse have become major factors affecting patient survival. Therefore, timely reconstitution of the immune system is crucial for the long-term survival of patients after hematopoietic stem cell transplantation. After myeloablation, transplant patients typically experience a period of pancytopenia lasting several days. Subsequently, innate immune cells, including granulocytes, monocytes / macrophages, and natural killer (NK) cells, largely recover within weeks after hematopoietic stem cell transplantation. In contrast, the recovery of adaptive immunity is much slower; typically, T cells and B cells take several months or even more than a year to return to normal after hematopoietic stem cell transplantation. If the reconstitution process is too long or poor, it may lead to relapse of hematological malignancies or infection by pathogenic microorganisms such as viruses. However, the mechanism of immune reconstitution after hematopoietic stem cell transplantation is not yet fully understood, and the factors affecting immune reconstitution still need further investigation.

[0003] Numerous studies have shown that stem cell source, pretreatment regimen, use of immunosuppressants, and the ages of both donor and recipient can influence immune reconstitution after hematopoietic stem cell transplantation. For example, autologous hematopoietic stem cell transplantation achieves faster T-cell immune reconstitution, especially CD4+, compared to allogeneic hematopoietic stem cell transplantation. + T cells and naive T cells; the naive T cell count in elderly donors was significantly lower than that in younger donors, and B cells were significantly reduced. Serum IgA and IgM levels in elderly donors were significantly lower 60 to 365 days after hematopoietic stem cell transplantation.

[0004] However, most current research on immune reconstitution after hematopoietic stem cell transplantation still focuses on descriptive analysis of relevant influencing factors, lacking in-depth research. Summary of the Invention

[0005] The purpose of this invention is to find drugs that can promote immune reconstitution after hematopoietic stem cell transplantation through in-depth research on immune reconstitution after hematopoietic stem cell transplantation.

[0006] Through long-term research and numerous experiments, the inventors have confirmed that the cytokine LYG1 can promote immune reconstitution after hematopoietic stem cell transplantation.

[0007] To achieve the above objectives, the present invention adopts the following technical solution:

[0008] The application of cytokine LYG1 in the preparation of drugs for promoting immune reconstitution after hematopoietic stem cell transplantation, or the application of cytokine LYG1 in the preparation of drugs for promoting immune reconstitution after hematopoietic stem cell transplantation.

[0009] Preferably, promoting immune reconstitution after hematopoietic stem cell transplantation includes promoting T-cell and B-cell immune reconstitution.

[0010] Preferably, promoting immune reconstitution after hematopoietic stem cell transplantation includes enhancing the number, proportion, and functional reconstitution of T cells or B cells.

[0011] Preferably, hematopoietic stem cell transplantation includes autologous and allogeneic hematopoietic stem cell transplantation.

[0012] Preferably, the prepared drug is injected into the human body before or after hematopoietic stem cell transplantation.

[0013] Preferably, the Gene ID of the cytokine LYG1 is 129530.

[0014] Preferably, the cytokine LYG1 is a recombinant LYG1 protein obtained by overexpression and purification.

[0015] The beneficial technical effect of this invention is that by injecting cytokine LYG1 into hematopoietic stem cell transplant patients, the patient's LYG1 cytokine levels are enhanced, which can promote immune reconstitution after hematopoietic stem cell transplantation. Attached Figure Description

[0016] Picture 1 AC represent CD4 in the immune reconstitution model. + T, CD8 + A schematic diagram illustrating the proportions of T cells and GC B cells in living lymphocytes;

[0017] Picture 1 DF stands for CD4 in the immune reconstitution model. + T, CD8 + A schematic diagram showing the absolute number of T cells and GC B cells. Detailed Implementation

[0018] LYG1 (Lysozyme G-like 1), a novel cytokine screened by Peking University First Hospital using immunomics technology (see Chinese patent document CN116585458), was found to have high expression levels in the kidneys and low expression levels in other tissues, including bone marrow. Furthermore, LYG1 exhibits the following characteristics: 1) It is a classic secreted protein with a small molecular weight, with the mature form approximately 20 kDa; 2) Although bioinformatics suggests that LYG1 belongs to the G-type lysozyme family, it does not possess lytic activity; 3) The recombinant LYG1 protein exhibits a clear dose-dependent effect and high efficacy. These characteristics are consistent with the characteristics of cytokine action.

[0019] The inventors constructed an immune reconstitution model using LYG1 knockout mice (KO) and control mice (WT): On day 0, 800 cGy was irradiated onto the KO and WT mice. Mice were administered 5 × 10⁵ KO or WT mice via tail vein infusion. 6 T-cell-removed bone marrow cells (TCD-BM) were used. Immune reconstitution of immune cells (T cells and B cells) was assessed 10 weeks after transplantation. Picture 1 AC displayed CD4 + T cells, CD8 + Statistics on the proportion of T cells and GC B cells in living lymph node cells (AC). Picture 1 CF displays CD4 + T cells, CD8 + Absolute counts of T cells and GC B cells (DF).

[0020] Table 1 shows the WT-WT, WT-KO, KO-WT, and KO-KO groups used in this invention to construct immune reconstitution models.

[0021] Division (group naming) donor recipient WT-WT WT WT WT-KO WT KO KO-WT KO WT KO-KO KO KO

[0022] Each group consisted of 5 mice. A p-value < 0.05 was considered statistically significant; * indicates p < 0.05, and ** indicates p < 0.01.

[0023] Compared to the KO-WT group, the KO-KO group had more reconstructed CD4 in mice. + T, CD8 + The ratio (AC) and absolute number (DF) of T cells and GC B cells were significantly reduced, indicating that the absence of LYG1 in the recipient can significantly inhibit the immune reconstitution of T cells and B cells after hematopoietic stem cell transplantation.

[0024] Similarly, compared to the WT-WT group, the WT-KO group had lower CD4 counts. + T, CD8 +The ratio (AC) and absolute number (DF) of T cells and GC B cells were also significantly reduced, indicating delayed immune reconstitution. This suggests that the absence of LYG1 in the recipient significantly inhibits immune reconstitution after hematopoietic stem cell transplantation.

[0025] Compared to the WT-KO group, the KO-KO group had CD4 reconstructed in mice. + T, CD8 + The ratio and absolute number of T cells and GC B cells showed a decreasing trend, but there was no significant difference, suggesting that the donor-derived LYG1 partially affects immune reconstitution, but the effect is not as great as the recipient's lack of LYG1.

[0026] Similarly, compared to the WT-WT group, the KO-WT group had lower CD4 counts. + T, CD8 + The ratio of T cells to GC B cells (AC) and their absolute number (DF) showed a decreasing trend, but there was no significant difference. This also suggests that the donor-derived LYG1 partially affects immune reconstitution, but the effect is not as great as the recipient's lack of LYG1.

[0027] By comparing the results of pairwise analyses across the four experimental groups, the inventors concluded that LYG1 deficiency significantly inhibits immune reconstitution after hematopoietic stem cell transplantation, and that the impact of recipient LYG1 deficiency on immune reconstitution after hematopoietic stem cell transplantation is more pronounced. Therefore, treatment with recombinant LYG1 protein in transplant recipients (i.e., patients) can accelerate immune reconstitution in patients.

[0028] Therefore, this invention develops the application of the cytokine LYG1 in promoting immune reconstitution after hematopoietic stem cell transplantation, specifically including:

[0029] A drug for promoting immune reconstitution after hematopoietic stem cell transplantation, wherein the active ingredient of the drug is the cytokine LYG1.

[0030] The application of cytokine LYG1 in the preparation of drugs for promoting immune reconstitution after hematopoietic stem cell transplantation, or the application of cytokine LYG1 in the preparation of drugs for promoting immune reconstitution after hematopoietic stem cell transplantation.

[0031] Preferably, promoting immune reconstitution after hematopoietic stem cell transplantation includes promoting T-cell and B-cell immune reconstitution.

[0032] Preferably, promoting immune reconstitution after hematopoietic stem cell transplantation includes enhancing the number, proportion, and functional reconstitution of T cells or B cells.

[0033] Preferably, hematopoietic stem cell transplantation includes autologous and allogeneic hematopoietic stem cell transplantation.

[0034] Preferably, the prepared drug is injected into the human body before or after hematopoietic stem cell transplantation.

[0035] Preferably, the Gene ID of the cytokine LYG1 is 129530.

[0036] Preferably, the cytokine LYG1 is a recombinant LYG1 protein obtained by overexpression and purification.

[0037] Although the present invention has been described in detail above, it is not limited thereto, and those skilled in the art can make various modifications based on the principles of the present invention. Therefore, all modifications made in accordance with the principles of the present invention should be understood to fall within the protection scope of the present invention.

Claims

1. Use of cytokine LYG1 in the preparation of a medicament for promoting immune reconstitution after hematopoietic stem cell transplantation.

2. The use according to claim 1, wherein the promoting immune reconstitution after hematopoietic stem cell transplantation comprises promoting T cell and B cell immune reconstitution.

3. The use according to claim 1, wherein the promoting immune reconstitution after hematopoietic stem cell transplantation comprises enhancing T cell or B cell cell number, proportion and functional reconstitution.

4. The use according to claim 1, wherein the hematopoietic stem cell transplantation comprises autologous and allogeneic hematopoietic stem cell transplantation.

5. The use according to claim 4, wherein the prepared medicament is injected into the patient before or after hematopoietic stem cell transplantation.

6. The use according to any one of claims 1-5, wherein the cytokine LYG1 has a Gene ID of 129530.

7. The use according to any one of claims 1-5, wherein the cytokine LYG1 is a LYG1 recombinant protein obtained by overexpression and purification.

8. A medicament for promoting immune reconstitution after hematopoietic stem cell transplantation, wherein the pharmacodynamic component of the medicament is cytokine LYG1.

9. The medicament according to claim 8, wherein the cytokine LYG1 has a Gene ID of 129530.

10. The medicament according to claim 8, wherein the cytokine LYG1 is a LYG1 recombinant protein obtained by overexpression and purification.

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