The spleen is the largest immune organ in the body, accounting for 25% of the total lymphoid tissue in the body. The spleen contains a large number of lymphocytes and macrophages , and is the center of the body's cellular immunity and humoral immunity . Analyzing the anatomical structure, all blood from the spleen enters the liver through the portal vein and . Compared with other organs in the body, the spleen has a more direct impact on liver immunity. Therefore, the spleen is expected to become a new therapeutic target for liver diseases. At the 4th "Belt and Road" International Symposium on Global Health and Silk Road University Alliance2022 Health Forum, Researcher Liu Pengfei of Professor Li Zongfang's team at the Second Affiliated Hospital of Xi'an Jiaotong University gave a presentation entitled " Liver Cirrhosis The report "The Spleen in the Process of : Revisiting Old Diseases with New Targets" launched an in-depth discussion around the "spleen-liver immune dialogue" and its clinical application prospects.
Researcher Liu Pengfei from Professor Li Zongfang’s team gave an online lecture
01 Regional immune characteristics of the liver
The liver is an important organ in the digestive system with metabolic functions in the body. It plays a key role in maintaining the body's internal environment homeostasis, oxidative stress balance, glycogen metabolism, and secretion. It plays important functions in protein synthesis and other aspects. 60%-80% of the cells in the liver are hepatocytes, while 20%-40% of the cells are "non-hepatocytes", including endothelial cells, , lymphocytes, Kupffer cells, etc. Lymphocytes include B cells (6%), T cells (63%), and NK cells (31%) (Fig. 1).
Therefore, the liver can serve as a "non-professional" regional immune organ. In particular, lymphocytes in the liver sinusoids can be in close contact with innate immune cells and sinusoidal endothelial cells, and accept their antigen presentation to generate a response. In addition, the liver also recruits immune cells from the periphery and other immune organs. Especially during the occurrence of liver diseases, the liver can effectively recruit immune cells and "educate" them in the liver microenvironment. These basic theories also laid an important foundation for the study of liver regional immunity.
In recent years, although there have been many reports on immunological phenomena related to the liver, research on the regional immune characteristics of the liver is still in its infancy. The natural immune dominance of the liver and the formation of immune tolerance, liver immunity and other immune organs and even the whole body The connection between immunity and the relationship between liver immunity and liver and even systemic diseases still need to be further studied.
Figure 1. Proportions of different types of cells in the liver (quoted from the report slide)
02 The spleen plays an important role in the occurrence and development of liver diseases
As the largest peripheral immune organ , the spleen participates in the peripheral circulation and will respond to disease when the disease occurs. Directly output immune cells or cytokine , or act as an extramedullary hematopoietic site to regulate blood cell production, affecting the progression of various diseases and playing an important role in body immunity. In recent years, studies have shown that the malignant transformation process from hepatitis and cirrhosis to liver cancer is often accompanied by hypersplenism in patients. At the same time, clinical studies have shown that hypersplenism is an independent risk factor for the development of hepatitis and cirrhosis into liver cancer, and splenectomy can effectively reverse the reduction of white blood cells and platelets in patients, reduce viral load, improve liver regional immune characteristics, and relieve symptoms. liver cirrhosis and reduce the risk of liver cancer.
Professor Li Zongfang’s team further research found that: compared with normal spleen, the number of germinal center in the spleen of patients with liver cirrhosis, portal hypertension and hypersplenism was significantly increased; the proportion of regulatory T cells and macrophages in the patient’s spleen was significantly increased, and the effect There was a decrease in T cells, and the proportion of cells expressing PD-1 increased (Figure 2); at the same time, the density of macrophages in the patient's spleen was significantly reduced. Compared with normal spleen macrophages, the phagocytosis of the patient's macrophages was Ability, effector cytokine secretion ability, antigen presentation ability, etc. are all in a state of overactivation.
Figure 2. Differences in the spleen between patients with liver cirrhosis, portal hypertension, hypersplenism and healthy people (quoted from the report slide)
In addition, Professor Li Zongfang’s team also conducted a follow-up analysis of the peripheral blood of patients with portal hypertension and hypersplenism who underwent splenectomy and found that : 2 weeks or even 2 months after the operation, the patient's immune disorder improved, the proportion of CD8+T cells increased, and the proportion of regulatory T cells decreased (Figure 3). Therefore, during the development of liver diseases (cirrhosis, portal hypertension, hypersplenism, and liver cancer), the immune function of the spleen gradually changes. Splenectomy is conducive to the normalization of the body's immunity. Splenic immunity plays an important role in the occurrence and development of liver diseases.
Figure 3. The therapeutic effect of splenectomy on patients with portal hypertension and hypersplenism (quoted from the report slide)
03 There is an "immune dialogue" between the spleen and the liver
In recent years, studies have provided evidence that spleen immune cells will migrate to the diseased liver. , participates in liver immune regulation, thereby affecting the progression of liver disease. Professor Li Zongfang’s team took the liver fibrosis model as an example to conduct relevant research. The research results show that in the process of liver fibrosis, the spleen has a role in promoting liver fibrosis, and this role may be related to the spleen promoting the infiltration of mononuclear phagocytes , especially M1 cells, in the liver; at the same time, in In liver fibrosis models, spleen macrophages will migrate to the liver and further promote the secretion of CCL2 by liver mononuclear macrophages, and the CCL2 secreted by liver mononuclear macrophages will have subsequent chemotactic effects on spleen macrophages.
It can be seen that there is an "immune dialogue" between the spleen and the liver. This "immune dialogue" plays an important role in the occurrence and development of liver diseases. It also provides new targets for the treatment of traditional liver diseases (Figure 4 ).
Figure 4. "Immune dialogue" between spleen and liver (quoted from the report slide)
04 Summary and clinical outlook
In general, the research results of Professor Li Zongfang's team, from the perspective of immunology, at the cellular and molecular levels It further revealed the "spleen-liver dialogue" and the new regulatory mechanism of related liver disease progression, giving the field a deeper understanding of the role of the spleen in liver disease; at the same time, the regional immunological characteristics and cells of the spleen and liver Basic and cutting-edge research on molecular regulatory networks reveals the interconnection between the spleen and liver in the occurrence of liver diseases, and also provides a more powerful basis for the treatment of the spleen in the treatment of liver diseases.
This multi-level and multi-pathway analysis will develop new target cells and molecules for the treatment of traditional chronic liver diseases . At the same time, comprehensive conditioning of the spleen through non-surgical therapy is also expected to gradually develop into a new clinical therapy for traditional liver disease treatment. Therefore, 's concept of "regulating the spleen and treating the liver" will not only lay the foundation for systematic research on tissue regional immunity, but will also vigorously promote the clinical transformation of subsequent research results.
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Expert profile
Li Zongfang
Professor, chief physician, doctoral supervisor. President of the Second Affiliated Hospital of Xi'an Jiaotong University, director of the National and Local Joint Engineering Research Center for Biodiagnosis and Treatment and Shaanxi Provincial Engineering Research Center for Biotherapy and Translational Medicine, and director of the Shaanxi Provincial Clinical Medical Research Center for Liver and Spleen Diseases. "Millions of Talents in the New Century" National-level candidate, winner of the "Chinese Physician Award", National Health Commission's "Tribute Expert", expert enjoying the State Council's special allowance, Shaanxi Province Sanqin Talent Allowance expert, Shaanxi Province "Three Five Talents" ”, a well-known expert in hepatobiliary surgery in China.
is currently a member of the International Hepatobiliary and Pancreatic Association; member of the Surgical Society of the Chinese Medical Association, deputy leader of the spleen function and spleen surgery group; chairman of the Xi'an Surgical Society of the Chinese Medical Association; deputy chairman of 8 professional committees including the Shaanxi Laparoscopic Surgery Society Committee.Deputy editor-in-chief of "Chinese Experimental Surgery", "International Surgery", and "Western Medicine", and editorial board member of more than 10 magazines including "Chinese Medical Journal (English Edition)" and "Chinese General Surgery". He is an expert in the second review of the National Natural Science Foundation and the Ministry of Education Fund, a member of the evaluation committee of the Chinese Medical Science and Technology Award and the Shaanxi Provincial Science and Technology Award, and a member of the expert database of the Chinese Medical Association, Shaanxi Province and Xi'an Medical Accident Appraisal Committee. Chief editor and deputy editor of 12 textbooks and monographs planned by national colleges and universities and the Ministry of Health. Published more than 200 papers. Among them, there are more than 100 SCI papers, and the first author has won 6 awards including the first and second prizes of Shaanxi Provincial Science and Technology Award. Supervise more than 60 master's and doctoral students.
Expert profile
Liu Pengfei
Researcher, doctoral supervisor. Selected in Xi'an Jiaotong University's "Youth Top Talent Support Program", member of the American Society of Toxicology (SOT), member of the Standing Committee of the Translational Medicine Youth Committee of the Shaanxi Provincial Anti-Cancer Association, communication review expert of the National Natural Science Foundation of China, and project review expert of the Shaanxi Provincial Department of Science and Technology , business manager of "Xi'an International Science and Technology Cooperation Base" (International Science and Technology Cooperation Base for Cellular Stress and Disease Diagnosis and Treatment). In recent years, he has been mainly engaged in research work related to "oxidative stress and liver and spleen metabolic diseases". He has published more than 60 academic papers in domestic and foreign journals. As the first author or corresponding author, he has published a series of academic journals such as Hepatology, PNAS and Redox Biology and other academic journals. Treatise.
