The human liver is usually perceived as a non-immunological organ engaged primarily in metabolic, nutrient storage and detoxification activities. However, we now know that the healthy liver is also a site of complex i...The human liver is usually perceived as a non-immunological organ engaged primarily in metabolic, nutrient storage and detoxification activities. However, we now know that the healthy liver is also a site of complex immunological activity mediated by a diverse immune cell repertoire as well as non-hematopoietic cell populations. In the nondiseased liver, metabolic and tissue remodeling functions require elements of inflammation. This inflammation, in combination with regular exposure to dietary and microbial products, creates the potential for excessive immune activation. In this complex microenvironment, the hepatic immune system tolerates harmless molecules while at the same time remaining alert to possible infectious agents, malignant cells or tissue damage. Upon appropriate immune activation to challenge by pathogens or tissue damage, mechanisms to resolve inflammation are essential to maintain liver homeostasis. Failure to clear ＇dangerous＇ stimuli or regulate appropriately activated immune mechanisms leads to pathological inflammation and disrupted tissue homeostasis characterized by the progressive development of fibrosis, cirrhosis and eventual liver failure. Hepatic inflammatory mechanisms therefore have a spectrum of roles in the healthy adult liver; they are essential to maintain tissue and organ homeostasis and, when dysregulated, are key drivers of the liver pathology associated with chronic infection, autoimmunity and malignancy. In this review, we explore the changing perception of inflammation and inflammatory mediators in normal liver homeostasis and propose targeting of liver-specific immune regulation pathways as a therapeutic approach to treat liver disease.展开更多
This review summarizes research discoveries within 4 areas of exercise immunology that have received the most attention from investigators :(1) acute and chronic effects of exercise on the immune system,(2) clinical b...This review summarizes research discoveries within 4 areas of exercise immunology that have received the most attention from investigators :(1) acute and chronic effects of exercise on the immune system,(2) clinical benefits of the exercise—immune relationship,(3) nutritional influen?ces on the immune response to exercise, and(4) the effect of exercise on immunosenescence. These scientific discoveries can be organized into distinctive time periods: 1900-1979, which focused on exercise-induced changes in basic immune cell counts and function; 1980-1989, during which seminal papers were published with evidence that heavy exertion was associated with transient immune dysfunction, elevated inflammatory biomarkers,and increased risk of upper respiratory tract infections; 1990-2009, when additional focus areas were added to the field of exercise immunology including the interactive effect of nutrition, effects on the aging immune system, and inflammatory cytokines; and 2010 to the present, when technological advances in mass spectrometry allowed system biology approaches(i.e., metabolomics, proteomics, lipidomics, and microbiome characterization) to be applied to exercise immunology studies. The future of exercise irmmunology will take advantage of these technologies to provide new insights on the interactions between exercise, nutrition, and immune function, with application down to the person?alized level. Additionally, these methodologies will improve mechanistic understanding of how exercise-induced immune perturbations reduce the risk of common chronic diseases.展开更多
基金We acknowledge funding from Science Foundation Ireland （grant # 12/IA/1667） and the Health Research Board （grant # HRA-POR-2013- 424）. In addition, we gratefully acknowledge the on-going research contributions from the Liver Transplant Unit at St. Vincent＇s University Hospital.
文摘The human liver is usually perceived as a non-immunological organ engaged primarily in metabolic, nutrient storage and detoxification activities. However, we now know that the healthy liver is also a site of complex immunological activity mediated by a diverse immune cell repertoire as well as non-hematopoietic cell populations. In the nondiseased liver, metabolic and tissue remodeling functions require elements of inflammation. This inflammation, in combination with regular exposure to dietary and microbial products, creates the potential for excessive immune activation. In this complex microenvironment, the hepatic immune system tolerates harmless molecules while at the same time remaining alert to possible infectious agents, malignant cells or tissue damage. Upon appropriate immune activation to challenge by pathogens or tissue damage, mechanisms to resolve inflammation are essential to maintain liver homeostasis. Failure to clear ＇dangerous＇ stimuli or regulate appropriately activated immune mechanisms leads to pathological inflammation and disrupted tissue homeostasis characterized by the progressive development of fibrosis, cirrhosis and eventual liver failure. Hepatic inflammatory mechanisms therefore have a spectrum of roles in the healthy adult liver; they are essential to maintain tissue and organ homeostasis and, when dysregulated, are key drivers of the liver pathology associated with chronic infection, autoimmunity and malignancy. In this review, we explore the changing perception of inflammation and inflammatory mediators in normal liver homeostasis and propose targeting of liver-specific immune regulation pathways as a therapeutic approach to treat liver disease.
文摘This review summarizes research discoveries within 4 areas of exercise immunology that have received the most attention from investigators :(1) acute and chronic effects of exercise on the immune system,(2) clinical benefits of the exercise—immune relationship,(3) nutritional influen?ces on the immune response to exercise, and(4) the effect of exercise on immunosenescence. These scientific discoveries can be organized into distinctive time periods: 1900-1979, which focused on exercise-induced changes in basic immune cell counts and function; 1980-1989, during which seminal papers were published with evidence that heavy exertion was associated with transient immune dysfunction, elevated inflammatory biomarkers,and increased risk of upper respiratory tract infections; 1990-2009, when additional focus areas were added to the field of exercise immunology including the interactive effect of nutrition, effects on the aging immune system, and inflammatory cytokines; and 2010 to the present, when technological advances in mass spectrometry allowed system biology approaches(i.e., metabolomics, proteomics, lipidomics, and microbiome characterization) to be applied to exercise immunology studies. The future of exercise irmmunology will take advantage of these technologies to provide new insights on the interactions between exercise, nutrition, and immune function, with application down to the person?alized level. Additionally, these methodologies will improve mechanistic understanding of how exercise-induced immune perturbations reduce the risk of common chronic diseases.
