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@#Diabetes mellitus can increase the risk and severity of periodontitis and may be associated with changes in the immune characteristics of periodontal tissues. In this paper, the morphological and immune characteristics of periodontal tissues in diabetic patients were reviewed in terms of the changes of morphology, structure and local immune cells in periodontal tissues caused by hyperglycemia and their regulatory mechanisms.
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AIM: To explore the key genes related to immunity and immune cell infiltration levels in diabetes retinopathy(DR)using bioinformatics.METHODS: Differential expression genes(DEGs)were obtained by “limma” R from Gene Expression Omnibus(GEO)data from September to October 2022, Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)were analyzed, and the infiltration of immune cell types in each sample was calculated based on CIBERSORT algorithm. Weighted gene co-expression network analysis(WGCNA)was used to screen for DEGs in immune-related gene modules. The protein-protein interaction(PPI)network was established by STRING online database and Cytoscape, and the hub genes were screened by MCODE and cytoHubba plug-ins.RESULTS: The results showed that 1 426 up-regulated and 206 down-regulated differential genes were screened, where 7 immune cell types, including B cell naive, Plasma cells, CD4+T cells, T cells regulatory(Tregs), Macrophages M0, Macrophages M1 and Neutrophils were significantly overexpressed(P<0.05), while others were low expressed(P<0.05). After WGCNA, a total of 820 DEGs were found in the modules most related to immunity. After constructing the PPI network, 10 key genes were screened using plug-ins, and two key genes were further screened using the expression amount of each differential gene in PPI: DLGAP5 and AURKB.CONCLUSION: This study used bioinformatics to screen the infiltration of immune cells and key genes related to immunity in patients with DR. These findings may provide evidences for future research, diagnosis, and treatment of DR.
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The relationship between tumor metabolism and immunity is complex and diverse. To date, the role of tumor-specific metabolic reprogramming in shaping the specific tumor microenvironment in tumor immunotherapy remains unclear. Lactic acid is the main product of glycolysis, and the aerobic glycolysis of tumor cells causes lactic acid to accumulate in the microenvironment. Recent studies have shown that the accumulation of lactic acid in the tumor microenvironment hinders anti-tumor immunity, especially affects the function, differentiation, and metabolism of immune cells, and participates in tumor immune escape, thus promoting tumor. This article reviews the effects of lactate accumulation in the tumor microenvironment on dendritic cells, T cells, NK cells, tumor-associated macrophages, and myeloid-derived suppressor cells. Targeted intervention of lactate production and efflux by tumor cells is expected to become a new strategy for tumor immunotherapy.
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Traditional Chinese medicine(TCM) has a long history and abundant experience in external therapy, which marks human wisdom. In the early history of human, people found that fumigation, coating, and sticking of some tree branches and herb stems can help alleviate scabies and remove parasites in productive labor, which indicates the emergence of external therapy. Pathogen usually enters the body through the surface, so external therapy can be used to treat the disease. External therapy is among the major characteristic of surgery of TCM. As one of the external therapies in TCM, external application to acupoints smooths the zang-fu organs through meridians and collaterals, thereby harmonizing yin and yang. This therapy emerged in the early society, formed the Spring and Autumn Period and the Warring States Period, improved in the Song and Ming dynasties, and matured in the Qing dynasty. With the efforts of experts in history, it has had a mature theory. According to modern research, it can avoid the first-pass effect of liver and the gastrointestinal irritation and improve the bioavailability of Chinese medicine. Based on the effect of Chinese medicine and the theory of meridian and collateral, it can stimulate the acupoints, exert regulatory effect on acupoints, and give full play to the efficacy of TCM and the interaction of the two. Thereby, it can regulate qi and blood and balance yin and yang, thus being widely used in the treatment of diseases. In this paper, the use of external application to acupoints, the effect on skin immunity, the regulation of neuro-inflammatory mechanism, the relationship between acupoint application and human circulation network, and the development of its dosage form were summarized through literature review. On this basis, this study is expected to lay a foundation for further research.
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Humans , Acupuncture Points , Biological Availability , Fumigation , Medicine, Chinese Traditional , MeridiansABSTRACT
Metastasis is the leading cause of cancer-related death. Despite extensive treatment, the prognosis for patients with metastatic cancer remains poor. In addition to conventional surgical resection, radiotherapy, immunotherapy, chemotherapy, and targeted therapy, various nanobiomaterials have attracted attention for their enhanced antitumor performance and low off-target effects. However, nanomedicines exhibit certain limitations in clinical applications, such as rapid clearance from the body, low biological stability, and poor targeting ability. Biomimetic methods utilize the natural biomembrane to mimic or hybridize nanoparticles and circumvent some of these limitations. Considering the involvement of immune cells in the tumor microenvironment of the metastatic cascade, biomimetic methods using immune cell membranes have been proposed with unique tumor-homing ability and high biocompatibility. In this review, we explore the impact of immune cells on various processes of tumor metastasis. Furthermore, we summarize the synthesis and applications of immune cell membrane-based nanocarriers increasing therapeutic efficacy against cancer metastases via immune evasion, prolonged circulation, enhanced tumor accumulation, and immunosuppression of the tumor microenvironment. Moreover, we describe the prospects and existing challenges in clinical translation.
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Cellular nanovesicles which are referred to as cell-derived, nanosized lipid bilayer structures, have emerged as a promising platform for regulating immune responses. Owing to their outstanding advantages such as high biocompatibility, prominent structural stability, and high loading capacity, cellular nanovesicles are suitable for delivering various immunomodulatory molecules, such as small molecules, nucleic acids, peptides, and proteins. Immunomodulation induced by cellular nanovesicles has been exploited to modulate immune cell behaviors, which is considered as a novel cell-free immunotherapeutic strategy for the prevention and treatment of diverse diseases. Here we review emerging concepts and new advances in leveraging cellular nanovesicles to activate or suppress immune responses, with the aim to explicate their applications for immunomodulation. We overview the general considerations and principles for the design of engineered cellular nanovesicles with tailored immunomodulatory activities. We also discuss new advances in engineering cellular nanovesicles as immunotherapies for treating major diseases.
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【Objective】 To investigate the expression of Kinesin family member 14 (KIF14), and its correlation with clinical prognosis and immune cell infiltration of clear cell renal cell carcinoma (ccRCC). 【Methods】 The correlation between KIF14 expression in ccRCC and different clinicopathological features were analyzed with TCGA, GEO and Ualcan databases. The correlation between KIF14 expression and prognosis was analzyed with Kaplan-Meier method. The correlation between KIF14 expression and immune cell infiltration was analzyed with TIMER. The protein-protein interaction network of KIF14 was conducted with Genemania. The co-expression genes of KIF14 in TCGA-KIRC were picked out in Linkedomics database and were used to perform GO annotations and KEGG pathway enrichment analysis with R software. The biological functions of KIF14 were verified with in vitro functional assay. 【Results】 KIF14 was highly expressed in ccRCC tissue and was positively correlated with clinical stage, pathological grade, and lymphatic metastasis, but negatively correlated with clinical prognosis. KIF14 expression was an independent risk factor for overall survival of ccRCC patients. GO annotations showed that KIF14 was involved in DNA replication, nuclear division, organelle fission, and cell adhesion. KEGG pathway enrichment analysis showed that KIF14 participated in cell cycle and p53 signaling pathway. Genemania analysis indicated KIF14 interacted with CENPE, CIT, KIF23, and other proteins. Timer showed that KIF14 was positively correlated with immune cell infiltration. Knockdown of KIF14 expression suppressed cell proliferation, migration, and invasion of ccRCC. 【Conclusions】 KIF14 may serve as a novel prognostic marker and a potential therapeutic target of clear cell renal cell carcinoma.
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【Objective】 To explore the effect of B lymphocytes on cardiac structure and function and myocardial immune cells during heart development. 【Methods】 Echocardiography, immunofluorescence staining and flow cytometry were used to evaluate the composition of immune cells of the heart and the cardiac structure and function in wild-type (WT) mice and B-lymphocyte-deficient (μMT) mice, respectively. 【Results】 Compared with those of μMT mice, the ratio of heart weight to mouse weight (P<0.05), left ventricular mass (P<0.05) and the cross-sectional area of myocardial cells WT mice were significantly increased, while the ventricular ejection fraction was significantly decreased (P<0.05). The results of mRNA sequencing showed that WT mice and μMT mice differentially expressed genes were mainly enriched in the signal pathway of heart development and hypertrophic cardiomyopathy. The results of flow cytometry showed that WT mice had more Ly6g+ neutrophils, CD4+ positive T cells (P<0.001) and CD8+T cells (P<0.05) compared with μMT mice. 【Conclusion】 B-lymphocyte depletion alters the composition of cardiomyocyte immune cells, reduces left ventricular mass, and increases myocardial contractility.
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The immune system plays a pivotal role in the pathogenesis and progression of diseases. Lipid peroxidation, as a key effector molecule in the execution of ferroptosis, exerts critical effects on the functionality and survival of various immune cells and is involved in the pathological processes of multiple diseases. There is accumulating evidence suggesting the presence of ferroptosis in immune cells as well. Lipid peroxidation is closely associated with immune cell function. Accumulation of lipid peroxidation products in immune cells can lead to ferroptosis, directly impacting immune cell function. Non-immune cells, through lipid peroxidation-mediated cell death, release signaling molecules that regulate immune cell function. They jointly influence the body's homeostasis. This article provides a comprehensive review of the latest research progress on the regulatory role of lipid peroxidation in immune function. It analyzes the relationship between lipid peroxidation and immune cells, and provides a theoretical foundation for potential strategies targeting cellular lipid peroxidation and immunotherapy in the treatment of diseases.
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Objective:To explore the prognostic biomarkers of glioblastoma (GBM) in the tumor microenvironment (TME) and its function.Methods:A total of 169 GBM samples of 161 GBM patients were collected from the Cancer Genome Atlas (TCGA) database. ESTIMATE algorithm in R4.1.0 software was used to calculate the proportion of immune components and stromal components in TME, which were expressed as immune score and stromal score, respectively. According to the median value of the two scores, 169 GBM samples were divided into the high score group and the low score group, respectively, 84 each in each group (those whose scores were equal to the median were not involved in the grouping). The differentially expressed genes (DEG) [false discovery rate (FDR) < 0.05] between the high score group and the low score group of the two scores were obtained by using limma package, and the co-up-regulated and co-down-regulated DEG of the two scores were obtained by using Venn program. Based on the STRING database, the protein interaction (PPI) network of co-up-regulated and down-regulated DEG of immune score and stromal score was constructed, and the top 30 genes with connectivity were selected. Univariate Cox proportional hazard model analysis of overall survival (OS) of 161 GBM patients in the TCGA database was performed on co-up-regulated and down-regulated DEG between immune score and stromal score by using R4.1.0 software to obtain the DEG affecting OS. The intersection of the DEG obtained from PPI analysis and Cox analysis was taken as the prognostic core genes. According to the median expression value of prognostic core genes in GBM samples from the TCGA database, 161 patients were divided into prognostic core genes high expression group and low expression group (patients whose scores were equal to the median were not involved in the grouping), with 80 cases in each group. Kaplan-Meier survival analysis of OS was performed by using R4.1.0 software. GSEA 4.2.1 software was used to perform gene set enrichment analysis (GSEA) on all genes with transcriptome data of GBM patients in the two groups of the TCGA databases, and the main enriched functions of the two groups of genes were obtained. The CIBERSORT algorithm was used to test the accuracy of the proportion of tumor infiltrating immune cell (TIC) subsets in 169 GBM samples from the TCGA database, and 57 GBM samples were finally obtained. Immune cells with differential expression levels and immune cells related to the expression of prognostic core genes among the samples with different expression levels of prognostic core genes were analyzed; Venn program was used to obtain the intersection of immune cells with differential levels and related immune cells, and differentially expressed TIC related to expressions of prognostic core genes in GBM were obtained.Results:Based on the immune score and stromal score of GBM samples in the TCGA database, a total of 693 co-up-regulated and co-down-regulated DEG of both scores were screened out. After the intersection of 78 DEG related to OS obtained by univariate Cox regression analysis and 30 DEG obtained by PPI network results, CC motif chemokine receptor 2 (CCR2) was identified as the prognostic core gene ( HR = 1.294, 95% CI 1.060-1.579, P = 0.011). GBM patients with CCR2 high expression had worse OS compared with those with CCR2 low expression ( P = 0.009). GSEA analysis showed that genes in the CCR2 high expression group were mainly enriched in immune-related pathways, while genes in the CCR2 low expression group were mainly enriched in metabolism-related pathways. Among 57 screened GBM samples, there were differences in the levels of 3 immune cells between the CCR2 high expression group and the CCR2 low expression group ( P < 0.05). CCR2 expression was correlated with the levels of 9 immune cells (all P < 0.05). Venn program analysis showed that differentially expressed 3 TIC in GBM related to CCR2 gene expression were obtained; among them, M2 macrophages were positively correlated with CCR2 expression, while T follicular helper cell and activated NK cells were negatively correlated with CCR2 expression. Conclusions:CCR2 may be the core gene related to the prognosis in the TME of GBM. As reference, the level of CCR2 can help to predict the status of TME and prognosis in GBM patients, which is expected to provide a new direction for the treatment of GBM.
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Objective:To investigate the clinical characteristics, treatment process and prognosis of children with severe side effects after chimeric antigen receptor T cell immunotherapy(CAR-T), so as to provide evidence for timely intervention after CAR-T treatment.Methods:From June 1, 2015 to May 31, 2020, children with cytokine release syndrome(CRS)or immune cell related neurotoxicity syndrome(ICANS)who were treated with CAR-T therapy in our hospital and revealed severe effects transferred to PICU were included in the study, and their clinical course and multiple laboratory examination data were systematically analyzed.Results:Seventeen children showed CRS reaction and entered PICU after CAR-T therapy.The most common clinical symptoms were respiratory distress(13 cases) and circulatory disorder(10 cases), of which 7 cases were complicated with severe ICANS.Serum interferon -γ(IFN-γ)and interleukin-6(IL-6)levels significantly increased after CAR-T cell infusion, reaching the peak at (5.1±1.6)days.The serum levels of IFN-γ and IL-6 in children with severe CRS were significantly higher than those in children with mild CRS(all P<0.05). The level of serum IL-6 in children with high tumor load was significantly higher than that in children with low tumor load( P<0.05). The mortality rate of children with elevated level of serum TNF-α was higher(5/5 vs.3/11, P<0.05). Children with severe CRS were more likely to develop grade 4 ICANS(4/4 vs.0/3, P<0.05). The mortality rate of children with oxygenation index(P/F value)<200 mmHg(1 mmHg=0.133 kPa) was higher(5/5 vs.2/12, P<0.05). The vasoactive inotropic score[ M( Min, Max)] in the death group was significantly higher than that in survival group[29.5(14.0, 50.0) vs.1.5(0, 25.0), Z=8.000, P=0.027]. Conclusion:Serum IL-6 and IFN-γ are crucial causes of CRS.High tumor load is one of the factors causing high level of serum inflammatory factors.Respiration and circulation systems are the most frequently involved systems.Therefore, the evaluation indexes of these two systems can help us judge the prognosis of children.
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There is a broad and urgent need for the clinical application of anticancer nanomedicine in tumor therapy, but the complex biological barrier in solid tumors has always been the main obstacle to infiltrating nanomedicine into the tumor. The traditional design of nanomedicine based on enhanced permeability and retention (EPR) effect still has some limitations in tumor permeability, it is urgent to find other design theories. Therefore, this review summarizes two novel strategies, active transcytosis and immune cell-mediated tumor penetration, for promoting tumor penetration of anticancer nanomedicine.
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Objective:To study the performance of immune reconstitution in patients with chimeric antigen receptor (CAR)-T cell immunotherapy bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A total of 61 patients with acute B lymphocytic leukemia (B-ALL) who received CAR-T cell bridging allo-HSCT in Beijing Lu Daopei Hospital from August 2018 to December 2021 were enrolled, and the clinical medical records of the above patients were retrospectively analyzed. The average age was 14 (7, 30) years old, including 39 males and 22 females. 32 patients were treated with CAR-T cell immunotherapy(CAR-T Group) and 29 didn't with CAR-T cell immunotherapy(non-CAR-T group). The follow-up period was 561 (235,784) days. Multicolor flow cytometry was used to detect the peripheral blood lymphocyte subsets, i.e. total lymphocytes, T lymphocytes, helper T cells, cytotoxic T cells, B lymphocytes, NK cells, and Treg cell counts before transplantation and 1, 2, 3, 6, 8, 10, and 12 months after transplantation, to evaluate the immune reconstitution performance post allo-HSCT.Results:Serum globulin before transplantation: The IgA level in the CAR-T group was 0.18 (0.06, 0.49) g/L, which was lower than that of 1.03 (0.63, 1.56) g/L in the non-CAR-T group ( U=103.5, P<0.001). The IgG level in the CAR-T group was 5.54 (4.04, 7.09) g/L, lower than that of 6.78 (5.27, 9.26) g/L in the non-CAR-T group, ( U=1 298.5, P=0.017), and the IgM level in the CAR-T group was 0.18 (0.05, 0.30) g/L, lower than that of 0.40 (0.26, 0.71) g/L in the non-CAR-T group ( U=166.0, P<0.001). In the CAR-T group before transplantation, the absolute count of total lymphocyte in peripheral blood was 833.00 (335.00, 1 727.50) /μl, lower than that of 1 052.00 (545.75, 1 812.50) /μl in the non-CAR-T group ( U=404.0, P<0.001). The absolute count of T lymphocyte in the CAR-T group before transplantation was 686.00 (233.00, 1 307.00)/μl, lower than that of 860.00 (391.00, 1 419.75) /μl in the non-CAR-T group ( U=406.0, P<0.001). The absolute count of helper T lymphocytes in the CAR-T group was 146.00 (40.50, 327.50) /μl, lower than that of 162.50 (66.00, 384.75) /μl in the non-CAR-T group ( U=494.0, P=0.002). The absolute count of cytotoxic T lymphocytes in the CAR-T group was 343.00 (56.50, 924.00) /μl, lower than that of 478.00 (143.50, 992.25) /μl in the non-CAR-T group ( U=483.5, P=0.001). The absolute count of B lymphocytes in CAR-T group was 22.00 (6.00, 186.00) /μl, lower than that of 33.00 (8.00, 220.00) /μl in the non-CAR-T group ( U=498.0, P=0.002). And when two groups of patients were monitored after transplantation, there was no statistical difference in absolute cell counts of each immune cell subpopulation( P>0.05). Comparing the clinical features of the two groups, the pre-transplant history of the CAR-T group was 981.00 (368.50, 1 514.75) d, longer than that of 323.00 (167.50, 450.50) d in the non-CAR-T group ( U=263.0, P=0.004). The dose of rabbit anti-human thymic immunoglobulin (ATG) in the pretreatment protocol of patients in the CAR-T group was 5.00 (5.00, 7.50) mg/Kg, lower than that of 7.00 (5.00, 7.50) mg/kg in the non-CAR-T group ( U=288.5, P=0.018). The infusion dose of CD34 +cells in the CAR-T group was 5.91 (4.23, 6.02) ×10 6/kg, higher than that of 4.51 (4.00, 5.93)×10 6/kg in the non-CAR-T group ( U=291.0, P=0.012). The duration of the application of cyclosporine after transplantation in the CAR-T group was 167.00 (119.25, 299.50) d, which was shorter than that of 197.00 (102.50, 450.50) d in the non-CAR-T group ( U=421.0, P=0.001). Conclusions:For patients in CAR-T group with low immune function before transplantation, it may be possible to make them comparable to non-CAR-T group in immune reconstitution state by reducing the dose of pretreatment ATG, increasing the counts of CD34 + cells infusion in the graft, and discontinuing cyclosporine as soon as possible after transplantation.
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In recent years, the science and technology of organ transplantation have developed rapidly, which has been widely applied worldwide. However, multiple challenges remain to be resolved by clinicians, such as functional damage and immune rejection of transplant organs, immune deficiency caused by extensive use of immunosuppressants, chronic allograft dysfunction and adverse reactions. This article introduced relevant key research results published in 2021, taking the function and mechanism of immune cell subsets in the process of organ transplantation rejection or immune tolerance, and the research and application of new materials and drugs in organ transplantation as the main clues. The latest research progresses on regional immune response, especially the application of tissue-resident memory T cell in organ transplantation, were briefly summarized, and the future development of transplantation immunology was prospected.
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Immune tolerance after liver transplantation refers to discontinuing use of immunosuppressants in varying patterns and maintaining the long-term stability of liver function of the recipients. At present, immune tolerance may be achieved by passive immune tolerance, active operational immune tolerance and induced immune tolerance. Multiple clinical trials have confirmed the safety and feasibility of these approaches. Compared with adults, pediatric recipients undergoing liver transplantation have better potential of immune tolerance, especially the living donor liver transplant recipients. Nevertheless, it remains a challenge to predict whether a certain individual may achieve immune tolerance. In this article, research progresses on the characteristics of immune tolerance in pediatric recipients, induction of immune tolerance, operational immune tolerance, induced immune tolerance, screening of recipients and tolerance markers were reviewed, aiming to provide reference for the formulation of postoperative immunosuppressant regimens, reduce the overall exposure to immunosuppressants and lower the risk of adverse reactions induced by immunosuppressants in children undergoing liver transplantation.
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Echinococcosis is a zoonotic parasitic disease caused by Echinococcus infections, and this disorder may cause fibrosis of multiple vital organs, which may further progress into cirrhosis. Early-stage hepatic fibrosis is reversible, and unraveling the mechanisms underlying hepatic fibrosis induced by Echinococcus infections is of great significance for the prevention and treatment of early-stage hepatic fibrosis. Recently, the studies pertaining to hepatic fibrosis associated with Echinococcus infections focus on cytokines and immune cells. This review summarizes the advances in the mechanisms underlying host immune cells- and cytokines-mediated hepatic fibrosis in humans or mice following Echinococcus infections.
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In recent years, with the progress of research on the molecular mechanism of cell death, it has been discovered that there are many new types of programmed cell death, including non-apoptotic (10 types) and apoptotic (2 types), which are widely involved in the pathogenesis of infectious diseases and tumors. It is also a frontier research topic and provides new ideas for disease prevention and treatment. This article reviews the published literature on programmed cell death, focusing on the characteristics of cell necrosis, apoptosis, pyroptosis, ferroptosis, neutrophil inflammatory cell death (NETosis), cuproptosis, and widespread apoptosis (PANoptosis), as well as their relationship with infectious diseases.
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Zinc is one of the essential trace elements for human. It is essential for human health. In recent decades, the distribution and transport of zinc in human body have gradually become more evident. The immunomodulatory effects of zinc on the immune system have also been elucidated. Zinc is involved in regulating the cellular signaling pathways of immune cells and affecting the development of immune organs, the physiological state and function of immune cells and the secretion of cytokines. It is an indispensable element in the immune system and plays an important role in maintaining the integrity and stability of the immune system. This article briefly introduced the distribution and transportation of zinc in the human body, with the emphasis on the relationship between zinc and the development and function of immune cells.
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The quality of life of organ transplant recipients is closely correlated with immune status. Compared with those undergoing other solid organ transplantation, the long-term prognosis of lung transplant recipients is worse. The underlying immune mechanism is complex with both similarities and characteristics. Therefore, in-depth understanding of the immune mechanism in the process of immune response of allogeneic lung transplantation plays a critical role in improving the long-term survival of the recipients. In this article, the unique composition of immune cells in the lung, the characteristics of rejection after lung transplantation, the early warning and differential diagnosis of pathogen infection in lung transplantation and postoperative complications after lung transplantation were investigated. Research progress on clinical diagnosis and basic studies related to immunology in allogeneic lung transplantation were summarized, aiming to elucidate the immunological characteristics of lung transplantation and provide theoretical basis for improving the longterm survival of lung transplant recipients and prevention and treatment of allograft dysfunction.
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Trogocytosis is a process of exchanging part of the membrane fragment or cytoplasmic content of cells through direct contact, and it's an interaction mechanism that exists between cells. Immune cell can obtain some characteristics of other cells through trogocytosis, and the new cells generated through trogocytosis may play an important role in the induction of graft immune tolerance. In this article, the origin and development of research on cell trogocytosis, mechanism of cell trogocytosis and biological significance of trogocytosis of immune cell were reviewed.