Development of vascular disease models to explore disease causation and pathomechanisms of rare vascular diseases
AbstractAs the field of medicine is striving forward heralded by a new era of next-generation sequencing (NGS) and integrated technologies such as bioprinting and biological material development, the utility of rare monogenetic vascular disease modeling in this landscape is starting to emerge. With their genetic simplicity and broader applicability, these patient-specific models are at the forefront of modern personalized medicine. As a collective, rare diseases are a significant burden on global healthcare systems, and rare vascular diseases make up a significant proportion of this. High costs are due to a lengthy diagnos...
Source: Seminars in Immunopathology - March 1, 2022 Category: Pathology Source Type: research
Adaptive immunity, chronic inflammation and the clock
AbstractThe adaptive arm of the immune system facilitates recognition of specific foreign pathogens and, via the action of T and B lymphocytes, induces a fine-tuned response to target the pathogen and develop immunological memory. The functionality of the adaptive immune system exhibits daily 24-h variation both in homeostatic processes (such as lymphocyte trafficking and development of T lymphocyte subsets) and in responses to challenge. Here, we discuss how the circadian clock exerts influence over the function of the adaptive immune system, considering the roles of cell intrinsic clockwork machinery and cell extrinsic r...
Source: Seminars in Immunopathology - March 1, 2022 Category: Pathology Source Type: research
Development of vascular disease models to explore disease causation and pathomechanisms of rare vascular diseases
AbstractAs the field of medicine is striving forward heralded by a new era of next-generation sequencing (NGS) and integrated technologies such as bioprinting and biological material development, the utility of rare monogenetic vascular disease modeling in this landscape is starting to emerge. With their genetic simplicity and broader applicability, these patient-specific models are at the forefront of modern personalized medicine. As a collective, rare diseases are a significant burden on global healthcare systems, and rare vascular diseases make up a significant proportion of this. High costs are due to a lengthy diagnos...
Source: Seminars in Immunopathology - March 1, 2022 Category: Pathology Source Type: research
Adaptive immunity, chronic inflammation and the clock
AbstractThe adaptive arm of the immune system facilitates recognition of specific foreign pathogens and, via the action of T and B lymphocytes, induces a fine-tuned response to target the pathogen and develop immunological memory. The functionality of the adaptive immune system exhibits daily 24-h variation both in homeostatic processes (such as lymphocyte trafficking and development of T lymphocyte subsets) and in responses to challenge. Here, we discuss how the circadian clock exerts influence over the function of the adaptive immune system, considering the roles of cell intrinsic clockwork machinery and cell extrinsic r...
Source: Seminars in Immunopathology - March 1, 2022 Category: Pathology Source Type: research
Th17 cells in the liver: balancing autoimmunity and pathogen defense
AbstractIn addition to carcinogenesis, T helper 17 (Th17) cells (a subtype of CD4 + T lymphocytes) are involved in the acute, chronic, and cirrhotic phases of liver diseases; however, their role in the development and progression of liver diseases remains unclear. It is difficult to elucidate the role of Th17 cells in liver diseases due to their dichotomous nature, i.e., pla sticity in terms of pathogenic or host protective function depending on environmental and time phase factors. Moreover, insufficient depletion of Th17 cells by inhibiting the cytokines and transcription factors involved in their production causes ...
Source: Seminars in Immunopathology - February 24, 2022 Category: Pathology Source Type: research
The role of circadian clock pathways in viral replication
AbstractThe daily oscillations of bi
ological and behavioural processes are controlled by the circadian clock circuitry that drives the physiology of the organism and, in particular, the functioning of the immune system in response to infectious agents. Circadian rhythmicity is known to affect both the pharmacokinetics and pharmacodynamics of pharmacological agents and vaccine-elicited immune responses. A better understanding of the role circadian pathways play in the regulation of virus replication will impact our clinical management of these diseases. This review summarises the experimental and clinical evidence on th...
Source: Seminars in Immunopathology - February 22, 2022 Category: Pathology Source Type: research
Cellular senescence in the cholangiopathies: a driver of immunopathology and a novel therapeutic target
AbstractThe cholangiopathies are a group of liver diseases that affect cholangiocytes, the epithelial cells that line the bile ducts. Biliary atresia (BA), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) are three cholangiopathies with significant immune-mediated pathogenesis where chronic inflammation and fibrosis lead to obliteration of bile ducts and eventual liver cirrhosis. Cellular senescence is a state of cell cycle arrest in which cells become resistant to apoptosis and profusely secrete a bioactive secretome. Recent evidence indicates that cholangiocyte senescence contributes to the pat...
Source: Seminars in Immunopathology - February 17, 2022 Category: Pathology Source Type: research
Mechanisms of vascular inflammation in deficiency of adenosine deaminase 2 (DADA2)
AbstractDeficiency of adenosine deaminase 2 (DADA2) was first described as a monogenic form of systemic vasculitis that closely resembles polyarteritis nodosa (PAN). The phenotypic spectrum of DADA2 has vastly expanded in recent years and now includes pure red cell aplasia, bone marrow failure syndrome, lymphoproliferative disease, and humoral immunodeficiency. Vasculitis remains the most common presentation of DADA2, and treatment with tumor necrosis factor inhibitors (TNFi) has shown remarkable efficacy in preventing stroke and ameliorating features of systemic inflammation. The precise function of ADA2 has not been eluc...
Source: Seminars in Immunopathology - February 17, 2022 Category: Pathology Source Type: research
Cellular senescence in the cholangiopathies: a driver of immunopathology and a novel therapeutic target
AbstractThe cholangiopathies are a group of liver diseases that affect cholangiocytes, the epithelial cells that line the bile ducts. Biliary atresia (BA), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) are three cholangiopathies with significant immune-mediated pathogenesis where chronic inflammation and fibrosis lead to obliteration of bile ducts and eventual liver cirrhosis. Cellular senescence is a state of cell cycle arrest in which cells become resistant to apoptosis and profusely secrete a bioactive secretome. Recent evidence indicates that cholangiocyte senescence contributes to the pat...
Source: Seminars in Immunopathology - February 17, 2022 Category: Pathology Source Type: research
Mechanisms of vascular inflammation in deficiency of adenosine deaminase 2 (DADA2)
AbstractDeficiency of adenosine deaminase 2 (DADA2) was first described as a monogenic form of systemic vasculitis that closely resembles polyarteritis nodosa (PAN). The phenotypic spectrum of DADA2 has vastly expanded in recent years and now includes pure red cell aplasia, bone marrow failure syndrome, lymphoproliferative disease, and humoral immunodeficiency. Vasculitis remains the most common presentation of DADA2, and treatment with tumor necrosis factor inhibitors (TNFi) has shown remarkable efficacy in preventing stroke and ameliorating features of systemic inflammation. The precise function of ADA2 has not been eluc...
Source: Seminars in Immunopathology - February 17, 2022 Category: Pathology Source Type: research
Circadian regulation of innate immunity in animals and humans and implications for human disease
AbstractCircadian rhythms are 24-h oscillating variations in physiology generated by the core circadian clock. There is now a wide body of evidence showing circadian regulation of the immune system. Innate immune cells contain the molecular circadian clock which drives rhythmic responses, from the magnitude of the inflammatory response to the numbers of circulating immune cells varying throughout the day. This leads to rhythmic presentation of disease clinically, for example the classic presentation of nocturnal asthma or the sudden development of pulmonary oedema from acute myocardial infarction first thing in the morning...
Source: Seminars in Immunopathology - February 15, 2022 Category: Pathology Source Type: research
