Correlation Analysis Of Lumbar Disc Degeneration And Myeloid-Derived Suppressor Cells

Background: When the body is in pathological conditions-tumors,infections,inflammation or autoimmune diseases,the cytokines or inflammatory factors secreted under the conditions can not only block the normal differentiation of IMC,but also induce it to become a bone marrow-derived inhibitor myeloid-derived suppressor cells(MDSC),which are massively recruited,expanded and activated in the peripheral blood,bone marrow or tumor tissue of patients,and exert a certain immunosuppressive effect.MDSCs are a heterogeneous population of bone marrow-derived cells composed of myeloid progenitor cells,immature macrophages,immature granulocytes and immature dendritic cells.However,the intervertebral disc is an immune-privileged organ.Once the degeneration occurs and NP is exposed to the immune system in the body,it will lead to an autoimmune reaction.Therefore,intervertebral disc degeneration(IVDD)is an autoimmune disease.The role of MDSC in IVDD remains unclear.This study aimed to characterize specific subpopulations of MDSCs as potential indicators of disease progression and potential therapeutic targets in patients with lumbar disc herniation.Methods: Gene expression sequencing datasets of nucleus pulposus and control nucleus pulposus tissues of patients with lumbar intervertebral degeneration were collected on the NCBI public platform GEO,and the proportion of G-MDSCs was predicted with reference to the up-regulated genes in G-MDSCs as a reference.Peripheral blood was drawn from patients admitted to hospital for lumbar disc herniation and healthy volunteers,and flow cytometry was used to analyze MDSCs in different subsets of blood samples from healthy subjects and patients with lumbar disc herniation.All subjects underwent lumbar spine MRI,and the grade and severity of lumbar disc degeneration were assessed using the Pfirrmann grading scale standard.Correlation analysis was performed on the age,gender,and proportion of blood MDSCs in combination with degree classification.Then,the dimensionality reduction and visualization big data analysis method t-SNE and the cluster analysis method Flow SOM are used to analyze the data obtained by the Cyto Flex,and compare and verify the results of manual gating.Finally,we further analyzed the correlation between circulating MDSCs and the clinicopathological grade of LDH in patients.Results: The GEO database predicts that G-MDSCs are highly expressed in patients with lumbar disc herniation;the frequency of circulating granulocyte MDSCs(G-MDSCs)correlates with the Pfirrmann classification of stages III and IV in patients with lumbar disc herniation,whereas the percentage of mononuclear MDSCs(M-MDSCs)only increased.Regarding patient age and sex,they were independent of the frequency of circulating G-MDSCs and M-MDSCs;the results of the computer-aided analysis were consistent with the obtained by our manual gating.Conclusion: Our experimental results show that the occurrence of LDH leads to changes in the MDSC subpopulation in the circulating peripheral blood of patients,providing new clinical evidences for the treatment and pathogenesis mechanism of LHD.In addition,the change of immune cell subset aggravates the development of IVDD to a certain extent,and the frequency of circulation G-MDSCs in patients with clinical grade III and IV LDH increases with the degree of degeneration,and the determination of G-MDSCs subgroup can be used as an auxiliary examination item for LDH.It provides new ideas for in-depth reseach of the pathogenesis,diagnostic indicators and treatment methods of LHD.