Summary of basic research on liver transplantation in China of 2023 / 器官移植

Liver transplantation is the optimal treatment for end-stage liver disease and hepatocellular carcinoma, which can significantly improve clinical prognosis and quality of life of patients. However, multiple challenges, such as rejection, immune tolerance, shortage of donor liver, preservation of donor liver, ischemia-reperfusion injury and postoperative complications, <i>etc.</i>, limit the efficacy of liver transplantation in clinical practice. Research teams in China have made significant contributions to the basic research related to liver transplantation by making continuous efforts and combining the development of emerging technologies, interdisciplinary integration and other emerging fields. In this article, the frontier progress in the basic research of liver transplantation in 2023 was reviewed, highlighting the progress made by Chinese research teams in the basic research of liver transplantation, aiming to provide reference for promoting the integration of Chinese characteristics into the research of liver transplantation, accelerate the integration of Chinese liver transplantation research with international community, and promote further advancement of liver transplantation in China.

Research progress on programmed death 1 and its ligand as markers of immune tolerance after liver transplantation / 中华肝胆外科杂志

Programmed death 1 (PD-1)/PD-1 ligand (PD-L1) are important signaling molecules that mediate immunosuppression. This signaling pathway leads to the evading of tumor cells from immune surveillance and plays an adverse affect on anti-tumor immunity. For grafts, the activation of PD-1/PD-L1 signaling pathway also plays an important role in the its evasion from host immune attack and the formation of immune tolerance. PD-1/PD-L1 has been shown to regulate immune tolerance in corneal, heart and lung transplantation. Its role in liver transplantation, however, has yet to be elaborated. This article reviews the potential of PD-1/PD-L1 as a marker of immune tolerance after liver transplantation.

Clinical controversies over antiviral therapy for patients in the immune-tolerant phase of hepatitis B virus infection / 临床肝胆病杂志

To achieve the goal of “eliminating viral hepatitis as a public health hazard by 2030”， extensive screening， active prevention， and antiviral therapy are currently recommended for chronic hepatitis B virus （HBV） infection； however， no consensus has been reached on whether to initiate antiviral therapy for patients in the immune-tolerant phase of chronic HBV infection. Some experts believe that patients in the immune-tolerant phase tend to have a stable liver immune microenvironment， with a low risk of disease progression and poor response to treatment， and thus it is not recommended to initiate antiviral therapy. However， various other studies have shown that patients in the immune-tolerant phase still have inflammatory damage in the liver， with a risk of disease progression and a high level of cost effectiveness， and therefore， some experts suggest that antiviral therapy should be actively initiated for patients in the immune-tolerant phase. This article performs a literature review of the definition of patients in the immune-tolerant phase of chronic HBV infection and the advantages and disadvantages of antiviral therapy and conducts a preliminary analysis based on previous studies， in order to accumulate the evidence for whether to initiate antiviral therapy in the immune-tolerant phase of chronic HBV infection and lay a foundation for standardized clinical diagnosis and treatment of patients in the immune-tolerant phase.

The Influence of Shoutai Wan （寿胎丸） on Lactic Acid Content at the Maternal-Fetal Interface and Expression of Immune-Related Factors in Recurrent Miscarriage Model Mice / 中医杂志

ObjectiveTo explore the possible mechanisms of Shoutai Wan （寿胎丸） in treating recurrent miscarriage （RSA） from the perspective of immune tolerance under the acidic microenvironment at the maternal-fetal interface. MethodsFemale CBA/J mice were randomly divided into normal group， model group， progesterone group， and Shoutai Wan group， with 15 mice in each group. The mice in the normal group and model group were given 0.2 ml distilled water by gavage each day， the Shoutai Wan group given Shoutai Wan decoction 0.15 g/（10 g·d） by gavage， the progesterone group given progesterone tablets 0.44 mg/（10 g·d） by gavage. After gavage for 14 days， the mice were cohabited. Female CBA/J mice in the normal group were mated with male BALB/c mice at a ratio of 2∶1， and female CBA/J mice in the other groups were mated with male DBA/2 mice at a ratio of 2∶1 to establish the RSA mouse model. Vaginal smears were taken from the female mice the next morning， and the appearance of a large number of spermatozoa and the presence of a vaginal plug were considered as the first day of pregnancy. After the appearance of the plug， the mice were continued to be administered according to the previous method until the 10th day of pregnancy. On the 10th day of pregnancy， maternal-fetal interface tissues were collected from each group of mice， and lactate dehydrogenase colorimetric method was used to detect lactate （LA） content； qPCR method and Western blot method were used to detect the expression of immune-related factors interleukin-4 （IL-4）， interferon-gamma （IFN-γ）， transforming growth factor beta 1 （TGF-β1）， and forkhead box protein 3 （Foxp3） mRNA and protein； flow cytometry was used to detect the numbers of helper T lymphocyte 1 （Th1）， helper T lymphocyte 2 （Th2）， regulatory T cell （Treg）， classical macrophage （M1）， and alternative macrophage （M2）. The bivariate Pearson test was used to analyze the correlation between LA content and the numbers of Th1， Th2， Treg， M1， and M2 cells， as well as the correlation between LA content and the expression of IL-4， IFN-γ， TGF-β1， Foxp3 protein， and mRNA. ResultsOn the 10th day of pregnancy， compared with the normal group， the LA content decreased in the model group， and the expression of IL-4， TGF-β1， Foxp3 protein and mRNA in the maternal-fetal interface tissues decreased， while the expression of IFN-γ protein and mRNA increased. The numbers of Th1 and M1 cells increased， while the numbers of Th2， Treg， and M2 cells decreased （P＜0.05 or P＜0.01）. Compared with the model group， the LA content increased in the Shoutai Wan group and progesterone group. The expression of IL-4， TGF-β1， Foxp3 protein and mRNA in the maternal-fetal interface tissues increased， while the expression of IFN-γ protein and mRNA decreased. The numbers of Th1 and M1 cells decreased， while the numbers of Th2， Treg， and M2 cells increased （P＜0.05 or P＜0.01）. The LA content was positively correlated with the numbers of Th2， Treg， and M2 cells， and the expression of IL-4， TGF-β1， Foxp3 protein， and mRNA （P＜0.05 or P＜0.01）； the LA content was negatively correlated with the numbers of Th1， M1 cells， and the expression of IFN-γ protein and mRNA （P＜0.05 or P＜0.01）. ConclusionShoutai Wan may improve immune tolerance by regulating the expression of immune-related factors in the acidic microenvironment at the maternal-fetal interface of RSA model mice， thereby exerting its role in preventing miscarriage.

Application progress of mesenchymal stem cells in islet transplantation for type 1 diabetes mellitus / 器官移植

Islet transplantation is considered as one of the most effective approach for type 1 diabetes mellitus, although its efficacy is limited by several factors. Anoxia, stress and rejection occurring during the isolation, culturing and transplantation of islets may have impact on the outcome of the islet transplantation. Due to the biological properties such as anti-inflammation, angiogenetic promotion and immune regulation, mesenchymal stem cells (MSCs) are all the way focused by researchers. Additionally, exosome, a derivative of MSC, also plays an import role in regulating anoxia-induced oxidative stress modulation, angiogenetic promotion, and immune regulation. MSC-based islet transplantation may be a useful therapeutic tool in treating type 1 diabetes. Therefore, in this review, the potential effect of MSC prior and posterior to the operation of the islet transplantation, its clinical application as well as its limitations were reviewed, aiming to offer insights into the future application of islet transplantation in treating type 1 diabetes.

Research progress on the role of tolerogenic dendritic cells in immune tolerance of liver transplantation / 器官移植

Rejection after liver transplantation severely affects the survival of recipients. Long-term use of immunosuppressants is an important approach to prevent rejection, whereas it may cause toxic effects and increase the risk of adverse events such as systemic infection and tumor recurrence, etc. Therefore, before successful liver transplantation, how to induce individual immune tolerance of recipients and achieve complete or early withdrawal of postoperative immunosuppressants remains to be investigated by practitioners of organ transplantation. In recent years, certain progresses have been made in the mechanism of immune tolerance induced by tolerogenic dendritic cells in liver transplantation, and preliminary outcomes have been obtained in clinical trials. In this article, basic research and clinical application progress in the characteristics of tolerogenic dendritic cells, the mechanism underlying participating in liver immune microenvironment remodeling, and inducing immune tolerance in liver transplantation were reviewed, aiming to provide reference for the application of tolerogenic dendritic cells in immune tolerance of liver transplantation.

Murciélagos como vectores de enfermedades virales e impacto en la salud humana

Introducción: Los murciélagos se destacan por ser los únicos mamíferos voladores, con alrededor de 1 400 especies que cumplen un rol fundamental como controladores de plagas y polinizadores de plantas nocturnas. Sin embargo, su influencia sobre la salud humana se ha evidenciado cada vez más, en particular después del surgimiento de brotes epidémicos de enfermedades virales asociadas a estos mamíferos. Objetivo: Analizar la influencia de los murciélagos en la salud humana, centrándose en su papel como portadores de enfermedades virales y su potencial como reservorios y vectores de enfermedades. Métodos: Se realizó una revisión bibliográfica de la literatura utilizando descriptores MeSH y términos como: Animals, Wild Chiroptera, Virus Diseases, Zoonoses, Disease Vectors, Disease Reservoirs, Public Health, bats, Communicable Disease Control, Disease Outbreaks, Prevention and Control. Se revisaron 1 442 artículos en bases de datos y documentos oficiales, se seleccionaron las fuentes relevantes con Mendeley Desktop 1.19.4. y se obtuvieron al final 47 artículos. Resultados: Existen varias especies de murciélagos que pueden afectar la salud del ser humano y que albergan en especial virus de las familias Filoviridae, Coronaviridae y Paramixoviridae. Los murciélagos se consideran incubadoras óptimas para la propagación de virus debido a su sistema inmune único que lo hace resistente a estos agentes infecciosos. Conclusiones: La vigilancia y monitoreo de los murciélagos, junto con acciones de educación pública y una gestión adecuada de sus hábitats, son fundamentales para la detección temprana y prevención de la transmisión de nuevos virus de estos mamíferos a los humanos.

Introduction: Bats are the only flight mammals, with around 1,400 species playing critical roles as pest controllers and nocturnal plant pollinators. However, its impact on human health has become increasingly evident, especially after the appearance of epidemic outbreaks of viral diseases related to these mammals. Objetive: To analyze the influence of bats on human health, focusing on their role as carriers of viral diseases and their potential as reservoirs and vectors of diseases. Methods: A literature bibliographical review was conducted using MeSH descriptors and keywords such as: Animals, Wild Chiroptera, Virus Diseases, Zoonosis, Disease Vectors, Disease Reservoirs, Public Health, bats, Communicable Disease Control, Disease Outbreaks, Prevention and Control. 1442 articles in databases and official documents were reviewed, selecting the relevant sources with Mendeley Desktop 1.19.4., obtaining 47 articles at the end. Results: There are several species of bats that can affect human health and that mainly harbor viruses from the Filoviridae families, Coronaviridae and Paramyxoviridae. Bats are considered optimal incubators for the spread of the virus due to their unique immune system that makes them particularly resistant to these infectious agents. Conclusions: Surveillance and monitoring of bats, together with public education actions and proper management of their habitats, are essential for early detection and prevention of transmission of new viruses from these mammals to humans.

COVID-19 en las embarazadas. Riesgo de las complicaciones durante el embarazo y en el neonato / COVID-19 in pregnant women. Risk of complications during pregnancy and in the newborn

Sobre el tema COVID-19 se han publicado múltiples estudios que reflejan su elevada incidencia, transmisibilidad, morbilidad y mortalidad, con gran repercusión y severidad en los grupos poblacionales de riesgo. El embarazo no escapa a ello, y la inmunosupresión fisiológica que se presenta en esta condición, hace a la gestante y al neonato, ser más susceptibles a las enfermedades infecciosas. El objetivo de esta comunicación es profundizar en la fisiopatología y la repercusión de la enfermedad COVID-19 en las gestantes y el neonato, para mejorar el conocimiento relacionado con el tema, el cual repercutirá en un mejor manejo de estos pacientes. Para ello, se realizó una revisión de investigaciones publicadas en el período comprendido entre enero y diciembre de 2021, en las bases de datos: SciELO, SCOPUS, Medline, Dialnet, Cumed y Lilacs. De los 44 artículos obtenidos inicialmente, 33 cumplieron los criterios de inclusión.

Several studies on COVID-19 have been published reflecting its high incidence, transmissibility, morbidity and mortality, with great repercussions and severity in population groups at risk. Pregnancy does not escape from this, and the physiological immunosuppression that occurs in this condition makes the pregnant woman and the newborn more susceptible to infectious diseases. The objective of this communication is to deepen the pathophysiology and the repercussion of the COVID-19 disease in pregnant women and the newborn in order to improve knowledge related to the subject, which will have an impact on better management of these patients. For this, a review of research published between January and December 2021 was carried out in the databases such as SciELO, SCOPUS, Medline, Dialnet, Cumed and Lilacs. A number of 33 articles met the inclusion criteria from 44 initially obtained.

Study on the mechanism of VEGF inducing tolerogenic dendritic cells in oral squamous cell carcinoma / 口腔医学

Objective@#To investigate the mechanism of vascular endothelial growth factor(VEGF) inducing tolerogenic dendritic cells(DCs) in oral squamous cell carcinoma (OSCC).@*Methods@#The DCs were divided into four groups: Control group (DC), VEGF group (VEGF added into DC), Co-culture group (DC co-cultured with SCC7) and Anti-VEGF group (anti-VEGF antibody added into DC co-cultured with SCC7). Flow cytometry (FCM) was used to detect DC surface markers. To detect the effect of DC on proliferation activity of T lymphocyte, the experiment included five groups: Nc group (T lymphocyte), Control group (T lymphocyte added into DC), VEGF group (T lymphocyte + DC + VEGF), Co-culture group (T lymphocyte + DC + supernatant of SCC7) and Anti-VEGF group (T lymphocyte + DC + supernatant of SCC7 + anti-VEGF antibody). Subsequently, the mixed lymphocyte reaction(MLR) was conducted. The expression levels of indole-2, 3-doxygenase(IDO)and programmed cell death 1 ligand 1(PD-L1)in DC were detected by western blot, real time PCR and FCM respectively. For the cytotoxic lymphocyte (CTL) assay, SCC7 cells and CTLs were mixed and CTL-mediated SCC7 cells cytotoxicity was tested. The experiment included four groups: Control group (T lymphocyte + DC), IDO inhibition group (T lymphocyte + DC + IDO inhibitor), Anti-PD-L1 antibody group (T lymphocyte + DC + anti-PD-L1 antibody) and Combination group (T lymphocyte + DC + IDO inhibitor + anti-PD-L1 antibody). The SCC7 tumor-bearing mice treated with IDO inhibitor and the anti-PD-L1 antibody were sacrificed and the tumor inhibition rate and the spleen index were determined. @*Results@#Compared with Control group, exogenous VEGF or SCC7 co-culture inhibited the relative number of DC expressing CD11C, CD80, CD86, CD40 and MHC Ⅱ. The positive DCs were increased in the Anti-VEGF group compared with VEGF or Co-culture group. In VEGF or Co-culture group, the number of T cells stimulated by SCC7-pulsed DCs was decreased compared with Control group. However, the ability of Anti-VEGF group to induce T cell proliferation was significantly increased compared with VEGF or Co-culture group. Significantly increased expression of IDO and PD-L1 were observed in VEGF and Co-culture group. However, this was partially reversed by addition of anti-VEGF antibody into the co-culture system. Compared with Control group, the expressions of CD11C and CD86 in DC in both the IDO inhibition group and Anti-PD-L1 antibody group were increased, and were significantly higher in the Combination group compared with the single drug groups. The similar results were exhibited in MLR and CTL assay. In vivo, the results revealed that the tumors obtained from the mice in three experimental groups were smaller than those in the control group. Furthermore, the tumor volume of the Combination group was the smallest. The spleen index of each group was calculated and the results showed the spleen index of the three experimental groups was significantly higher than that of Control group.@*Conclusion@#VEGF in OSCC micro-environment inhibits the maturation and function of DC that are transformed into tolerogenic DC by high expression of IDO and PD-L1.

Transient elastography technology role assessment during the diagnosis and treatment of patients with chronic hepatitis B virus infection / 中华肝脏病杂志

Objective: To explore the role of transient elastography technology in the assessment of disease staging and treatment in patients with chronic hepatitis B virus (HBV) infection. Methods: Patients who were clinically diagnosed with chronic HBV infection at Beijing Tsinghua Changgung Hospital from January 2018 to December 2021 was collected. Liver stiffness measurement (LSM) examination was performed more than once by transient elastography. The count data were expressed as cases (%) and the χ (2) test was made. Fisher's exact test was used with theoretical frequency less than 5. The measurement data between two groups was compared by t-test. Multiple groups were compared with an analysis of variance. Results: 1 055 patients were included in this study, including 669 (63.4%) males and 386 (36.6%) females. 757 (71.8%) patients were untreated. Among the untreated patients, the LSM value in the immune clearance (10.2 ± 3.8) kPa (187 cases, 40.4%), and the reactivation stages (9.1 ± 3.4) kPa (114 cases, 24.6%) was significantly higher than that in the immune tolerance (8.7 ± 3.6) kPa (78 cases, 16.8%) and immune control stages (8.4 ± 3.5) KPa (84 cases, 18.1%), and the difference between the four groups was statistically significant (F = 5.31 and P = 0.03). With ALT (male: 30 U/L, female: 19 U/L) as defined the normal value, the LSM value in the immune tolerance and the immune control stages were (5.8 ± 0.9) kPa and (7.1 ± 2.5) kPa, respectively, which were significantly lower than those of patients in the immune tolerance and immune control stages, and the difference was statistically significant (P < 0.01). There were 294 (38.8%) patients with uncertain period, excluding patients with fatty liver. Patients with uncertain periods were divided into four gray zone (GZ) groups: immune tolerance stage: LSM (5.1 ± 1.3) kPa was significantly lower than GZ-A (6.5 ± 2.4) kPa, t = 2.06, P = 0.03, and the difference was statistically significant; immune control stage: LSM was (5.6 ± 1.5) kPa, which was also lower than GZ-C (6.8 ± 1.3) kPa, t = 3.08, P = 0.02, and the difference was statistically significant; immune clearance stage: LSM > 8.0 kPa. LSM values showed a year-by-year reduction in patients with expanded indications who started antiviral treatment and were followed up for three years. Conclusion: The LSM value is significantly lower after the decrease of the defined high-normal ALT value in patients with the immune tolerance and immune control stages of chronic HBV infection. The LSM values of GZ-A and GZ-C in the uncertain periods of chronic HBV infection are higher than those of patients in the immune tolerance and immune control stages.

Macrophages and kidney transplantation / 器官移植

Kidney transplantation is the optimal treatment for patients with end-stage renal disease, whereas long-term survival of renal allografts remains a challenging issue. Renal ischemia-reperfusion injury (IRI) and rejection of renal allografts are considered as important influencing factors of long-term survival of renal allografts, which are regulated by innate and adaptive immune cells. Macrophages are one type of innate immune cells that could assist initiating adaptive immunity and are divided into M1, M2 and regulatory macrophages. Previous studies have revealed that M1 macrophages may aggravate renal IRI and acute T cell-mediated rejection (TCMR). However, M2 macrophages may mitigate renal IRI and acute TCMR, whereas it is positively correlated with antibody-mediated rejection (AMR). Regulatory macrophages are a special subgroup of macrophages, which may induce immune tolerance in organ transplantation and have promising clinical application prospects and basic scientific research value. In this article, the relationship among macrophage typing, macrophages and renal IRI, rejection of renal allografts, regulatory macrophages and immune tolerance was reviewed, and the potential mechanism was analyzed, aiming to induce changes in macrophage subtypes or eliminate specific subtypes of macrophages, thereby improving clinical prognosis of the recipients and long-term survival of renal allografts.

Advances in application of regulatory T cells in transplant immune tolerance: from basic to clinical research / 器官移植

Regulatory T cells (Treg) are important inhibitory immune cells to establish immune tolerance, which play a pivotal role in regulating excessive immune response and autoimmune diseases of the host. Previous studies related to transplant immune tolerance have confirmed that increasing the number of Treg in vivo or enhancing the function of Treg serve as a therapeutic strategy to induce transplant immune tolerance. At present, Treg-based induction methods for transplant immune tolerance include adoptive infusion of Treg, in vivo amplification of Treg and utilization of antigen-specific Treg. In this article, the characteristics and mechanism of Treg, the latest research progress on basic experiments and clinical practice of Treg related to transplant immune tolerance at home and abroad were reviewed, and future challenges and development of Treg therapy were prospected, aiming to unravel the significance and application prospect of Treg in transplant immune tolerance, explore the advantages and limitations of Treg therapeutic strategies, and provide reference and evidence for subsequent research in this field.

Advances in butyrates and intestinal immune tolerance in children with cow′s milk protein allergy / 国际儿科学杂志

Cow′s milk protein allergy is common in infants, which is an abnormal immune reaction caused by the imbalance of intestinal immune tolerance system.Butyrates, the fermentation product of intestinal anaerobic bacteria, can be used as a histone deacetylase inhibitors and a ligand of G protein-coupled receptors to regulate intestinal innate immunity and adaptive immune function, thereby inducing intestinal immune tolerance in children with cow′s milk protein allergy, which has potential clinical therapeutic value for cow′s milk protein allergy.However, this theory is still only based on the exploration of mechanisms at the cellular and animal levels and has not been applied in the clinic.This article reviews the intestinal immune mechanism of cow′s milk protein allergy, the anabolism of butyrates and the important role of butyrates in intestinal immune tolerance of cow′s milk protein allergy, aiming to lay a theoretical foundation for further clinical application of butyrate-induced intestinal immune tolerance of cow′s milk protein allergy.

Chronic infection of hepatitis B virus and cellular immunity / 中华微生物学和免疫学杂志

The persistent infection of hepatitis B virus (HBV) is the result of lacking specific immunity against the virus. This state is also called immune tolerance to HBV. In most cases, acute HBV infection in adults can induce specific immune response which can clear the virus. Perinatal HBV infection, however, usually progresses to chronic infection, indicating a defect in HBV-specific immune response. A typical specific immune response includes four processes, which were antigen presentation, specific CD4 + T cell activation, specific CD8 + T cell activation and B cell activation. There must be some dysfunctions in some or all of the four processes during chronic HBV infection. This article discussed the relationship between chronic HBV infection and cellular immunity, hoping to provide a reference for further study on the reconstitution of specific immunity against HBV.

New Horizons in Treatment of Celiac Disease / 胃肠病学

Celiac disease is a common immune-mediated disorder that may present with various heterogeneous symptoms following gluten ingestion.It accounts for 0.7%-1.4%of the global population.The prevalence of celiac disease in China was once considered extremely low.However,in recent years,several cases of celiac disease have been reported one after another,which has gradually attracted people's attention.A gluten-free diet is the only effective treatment for celiac disease,but it has limitations in certain patient groups and is difficult to maintain over time.This is why studying alternative treatment options for celiac disease is of great clinical importance.In recent years,the treatment of celiac disease has seen the emergence of several novel therapies that provide ideas and directions for clinical treatment in terms of removing or reducing the factors that cause abnormalities in immune tolerance,suppressing one's immune response to gluten,and re-establishing immune tolerance to gluten.This review focuses on the research progress of new therapies for celiac disease.

Research and application progress in adoptive re-transfusion of regulatory cells in organ transplantation / 器官移植

Rejection and adverse reactions caused by long-term use of immunosuppressants severely affect the survival rate and quality of life of organ transplant recipients. Immune tolerance induction plays a key role in improving the survival rate and quality of life of organ transplant recipients. In recent years, tremendous progress has been achieved in adoptive re-transfusion of regulatory cells. In this article, research progress in regulatory T cell (Treg), myeloid-derived suppressor cell (MDSC) and regulatory B cell (Breg) in animal experiment and clinical application was reviewed, and the main clinical problems of adoptive re-transfusion of regulatory cells, the application of chimeric antigen receptor Treg and the concept of cell therapy in immune evaluation were summarized, aiming to deepen the understanding of regulatory cell therapy, promote the application of regulatory cells in immune tolerance of organ transplantation, and improve clinical efficacy of organ transplantation and the quality of life of recipients.

Application progress in the role of vitamin D3 in transplantation immunity / 器官移植

Vitamin D3 is a kind of vitamin that plays important roles in maintaining the normal physiological function of the human body, and its metabolites and analogues exhibit strong anti-inflammatory activity. Vitamin D3 could be activated and converted into 1α, 25-dihydroxyvitamin D3, a kind of steroid hormone, in the human body, which participates in the regulation of cellular metabolism by activating vitamin D receptor (a kind of transcription factor), thus exerting immunomodulatory effects. This is essential for maintaining the physiological health of the body. Currently, there is a growing number of studies that suggest important roles for 1α, 25-dihydroxyvitamin D3 in organ transplantation immunomodulation and tolerance. Therefore, we reviewed the overview and physiological effects of 1α, 25-dihydroxyvitamin D3, the immunomodulatory effects of vitamin D3 and the application of vitamin D3 in clinical organ transplantation, and summarized the value of applying vitamin D3 in inducing immune tolerance in transplantation, with the aim of providing a reference for promoting the application of vitamin D3 in transplantation immunity.

Prevention and treatment of chronic graft-versus-host disease by mesenchymal stem cells: advances and challenges / 器官移植

Chronic graft-versus-host disease (cGVHD) is the main complication after allogeneic hematopoietic stem cell transplantation, which is also the major cause of non-relapse -related death. Due to its complex pathophysiological process, the response rate of conventional glucocorticoids combined with immunosuppressants is less than 50%. Second-line therapy should be given for patients with glucocorticoid-resistant cGVHD. Nevertheless, no consensus has been reached on current second-line therapy and the therapeutic effect is relatively poor. Mesenchymal stem cell (MSC) is one of the most common adult stem cells. Due to multi-dimensional and multi-target immune regulating function, MSC has been widely applied in the prevention and treatment of cGVHD. In addition, accumulated studies have confirmed the safety and efficacy of MSC in the treatment of cGVHD, which is expected to become a novel strategy for the prevention and management of cGVHD. In this article, research progress, mechanism and existing problems of prevention and treatment of cGVHD by MSC were reviewed, aiming to provide novel ideas for optimizing therapeutic regimens of MSC and enhancing the prevention and treatment effect of cGVHD in subsequent research.

Anemia hemolítica autoinmune: mecanismos de inducción de autoinmunidad e inmunobiología / Autoimmune hemolytic anemia: mechanisms of autoimmunity induction and immunobiology

Introducción: La patogénesis de la anemia hemolítica autoinmune es un proceso complejo en el que muchos elementos tienen una función esencial que repercuten en la gran heterogeneidad clínica de la enfermedad, pero los mecanismos involucrados en su inducción se desconocen en gran medida. Objetivo: Explicar los principales mecanismos propuestos en el inicio y aparición de la anemia hemolítica autoinmune y su contribución a la fisiopatología de la enfermedad. Métodos: Se realizó una revisión de la literatura en los idiomas inglés y español, de artículos publicados en los últimos 10 años sobre mecanismos propuestos en el inicio de la anemia hemolítica autoinmune. Análisis y síntesis de la información: Los mecanismos propuestos en la inducción de la autoinmunidad contra los eritrocitos incluyen el mimetismo molecular entre antígenos endógenos y antígenos exógenos, el procesamiento desregulado de autoantígenos influenciado por factores adquiridos y la disfunción de los linfocitos B y T. Conclusiones: Los mecanismos propuestos en la aparición de la anemia hemolítica autoinmune brindan información valiosa para mejorar la comprensión de los mecanismos moleculares involucrados y subrayan la complejidad de los fenómenos involucrados en la perdida de la tolerancia hacia los eritrocitos autólogos y el delicado equilibrio entre factores genéticos y ambientales(AU)

Introduction: The pathogenesis of autoimmune hemolytic anemia is a complex process in which many elements play an essential role and have an impact on the great clinical heterogeneity of the disease, but the mechanisms involved in its induction are largely unknown. Objective: To explain the main mechanisms proposed in the initiation and occurrence of autoimmune hemolytic anemia and its contribution to the pathophysiology of the disease. Methods: A review of the literature, in English and Spanish languages, of articles published in the last 10 years on proposed mechanisms in the initiation of autoimmune hemolytic anemia was carried out. Analysis and synthesis of information: Proposed mechanisms for the induction of autoimmunity against erythrocytes include molecular mimicry between endogenous and exogenous antigens, deregulated processing of autoantigens influenced by acquired factors, and B and T cells dysfunction. Conclusions: The proposed mechanisms in the occurrence of autoimmune hemolytic anemia provide valuable information to improve the understanding of the mechanisms involved and underline the complexity of the phenomena involved in the loss of tolerance towards autologous erythrocytes and the delicate balance between genetic and environmental factors(AU)

The Possible Cure of Ulcerative Colitis based on the Hypothesis that Some Cancers are Rich Source of Non-Apoptotic and Functional Treg Cells

Many of the Autoimmune diseases, if not all, arise because either the levels of regulatory T cells (Tregs) have reduced in the milieu of organ affected or the Tregs in the milieu of organ affected have impaired.When the Tregs undergo either of these two fates, the conventional T cells wreck havoc on the healthy cells of the body, killing them and causing chronic inflammation. Such a state in the colon and rectum together is mostly the disease called Ulcerative Colitis (UC). It has been hypothesized that the impaired functioning of Tregs cause UC. Hence if the milieu of colon and rectum in the UC patients is populated with non-apoptotic fully functional Tregs, they can perhaps be cured. But from where to get such Tregs ? From the studies of Immunotherapies in Cancers I hypothesize that some cancers including the colitis-associated cancer can be the source of such Tregs. Based on these ideas I propose in this paper two possible curative therapies for UC which I call the CAR-Treg therapy and the E-Treg therapy. CAR-Treg therapy is based on the theory of multispecific Chimeric Antigen Receptors, and E-Treg therapy is based on the theory of cell encapsulation.