2007 George L. Duff Memorial Lecture—The Immune Response in Atherosclerosis

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Göran K. Hansson
Keyword(s):  
Innate Immunity ◽  
Vascular Inflammation ◽  
Experimental Studies ◽  
Memorial Lecture ◽  
Immune Reactions ◽  
Specific Antigens ◽  
Atherosclerotic Process ◽  
Molecular Patterns ◽  
Lipoprotein Retention

Immune responses participate in every phase of atherosclerosis. Indeed, atherosclerosis can be viewed as an immune/inflammatory response to lipoprotein retention in the artery wall. There is increasing evidence that both adaptive and innate immunity tightly regulate the atherosclerotic process. Specific antigens and pathogen-like molecular patterns initiate the 2 aspects of immunity by ligating T- and B-cell receptors and pattern recognition receptors, respectively. Effector responses of vascular immune reactions include macrophage activation, cellular immunity, antibody formation, and vascular inflammation. Whereas experimental studies in gene-targeted models have identified major roles for innate immunity and Th1 responses in plaque initiation and progression, clinical, epidemiological and genetic studies suggest that plaque activation, rupture, and atherothrombosis also depend on immune reactions. This lecture will focus on the role of immune mechanisms in the formation and activation of atherosclerotic plaques.

scholarly journals Insight Cross-talk between p53 and Toll-like Receptor

2021 ◽  
pp. 23-29
Author(s):  
Mohammad Jahoor Alam ◽  
Fevzi Bardakci ◽  
Sadia Anjum ◽  
Shumayla Rasheed Mir ◽  
Irfan Ahmad ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Transcription Factors ◽  
Cross Talk ◽  
Experimental Studies ◽  
Therapeutic Interventions ◽  
Toll Like Receptor ◽  
Transcription Activator ◽  
Molecular Patterns ◽  
Broad Understanding

Toll-like receptors (TLR) are one of the most-studied receptors for their role in innate immunity. TLRs are reported to binds with conserved pathogen-associated molecular patterns (PAMPS). TLRs and PAMPS interaction leads to several downstream proteins' activation, which further signaled to the various transcription factors. Moreover, these transcription factors play an important role in synthesizing proteins that control cellular immunity. Various TLR proteins have been reported in humans as well several other organisms. Studies show that apart from inducing innate immunity, TLRs have also played an important role in the induction of many proteins, and protein networks associated with initiation apoptosis and cancer prevention. P53 is one of the most important and widely studied proteins. Moreover, various experimental studies suggest that p53 has an important role as tumor suppressor. It is reported that more than 50% of cancerous growth are associated with the mutation of p53. It acts as transcription activator for several proteins that are mostly associated with glycolysis, cell cycle, cell differentiation, apoptosis and cancer. In the present review, we present an insight cross-talk between p53 and Toll-like receptor. In addition, the well-characterized role of p53 in the regulation of the immune system is studied, which would provide a new insight to the broad understanding of p53 role in human biology. Moreover, the association of the p53 and TLRs can lead to therapeutic interventions.

scholarly journals Regulatory T Cell-Enhancing Therapies to Treat Atherosclerosis

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 723
Author(s):  
Hafid Ait-Oufella ◽  
Jean-Rémi Lavillegrand ◽  
Alain Tedgui
Keyword(s):  
T Cell ◽  
Current Knowledge ◽  
Experimental Studies ◽  
Therapeutic Approaches ◽  
Coronary Patients ◽  
Cell Subpopulations ◽  
Atherosclerotic Process ◽  
T Cell Subpopulations ◽  
Disease Analysis

Experimental studies have provided strong evidence that chronic inflammation triggered by the sub-endothelial accumulation of cholesterol-rich lipoproteins in arteries is essential in the initiation and progression of atherosclerosis. Recent clinical trials highlighting the efficacy of anti-inflammatory therapies in coronary patients have confirmed that this is also true in humans Monocytes/macrophages are central cells in the atherosclerotic process, but adaptive immunity, through B and T lymphocytes, as well as dendritic cells, also modulates the progression of the disease. Analysis of the role of different T cell subpopulations in murine models of atherosclerosis identified effector Th1 cells as proatherogenic, whereas regulatory T cells (Tregs) have been shown to protect against atherosclerosis. For these reasons, better understanding of how Tregs influence the atherosclerotic process is believed to provide novel Treg-targeted therapies to combat atherosclerosis. This review article summarizes current knowledge about the role of Tregs in atherosclerosis and discusses ways to enhance their function as novel immunomodulatory therapeutic approaches against cardiovascular disease.

scholarly journals Evolving Perspectives on Innate Immune Mechanisms of IPF

2021 ◽  
Vol 8 ◽  
Author(s):  
Genta Ishikawa ◽  
Angela Liu ◽  
Erica L. Herzog
Keyword(s):  
Innate Immunity ◽  
Genetic Factors ◽  
Suppressor Cells ◽  
Innate Immune ◽  
Lymphoid Cells ◽  
Animal Modeling ◽  
Myeloid Suppressor Cells ◽  
Disease Outcomes ◽  
Molecular Patterns

While epithelial-fibroblast interactions are viewed as the primary drivers of Idiopathic Pulmonary Fibrosis (IPF), evidence gleaned from animal modeling and human studies implicates innate immunity as well. To provide perspective on this topic, this review synthesizes the available data regarding the complex role of innate immunity in IPF. The role of substances present in the fibrotic microenvironment including pathogen associated molecular patterns (PAMPs) derived from invading or commensal microbes, and danger associated molecular patterns (DAMPs) derived from injured cells and tissues will be discussed along with the proposed contribution of innate immune populations such as macrophages, neutrophils, fibrocytes, myeloid suppressor cells, and innate lymphoid cells. Each component will be considered in the context of its relationship to environmental and genetic factors, disease outcomes, and potential therapies. We conclude with discussion of unanswered questions and opportunities for future study in this area.

scholarly journals Role of Peroxisome Proliferator-Activated Receptor-γin Vascular Inflammation

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Kousei Ohshima ◽  
Masaki Mogi ◽  
Masatsugu Horiuchi
Keyword(s):  
Immune Cells ◽  
Adipocyte Differentiation ◽  
Therapeutic Potential ◽  
Vascular Inflammation ◽  
Experimental Studies ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Important Regulator ◽  
Artery Disease

Vascular inflammation plays a crucial role in atherosclerosis, and its regulation is important to prevent cerebrovascular and coronary artery disease. The inflammatory process in atherogenesis involves a variety of immune cells including monocytes/macrophages, lymphocytes, dendritic cells, and neutrophils, which all express peroxisome proliferator-activated receptor-γ(PPAR-γ). PPAR-γis a nuclear receptor and transcription factor in the steroid superfamily and is known to be a key regulator of adipocyte differentiation. Increasing evidence from mainly experimental studies has demonstrated that PPAR-γactivation by endogenous and synthetic ligands is involved in lipid metabolism and anti-inflammatory activity. In addition, recent clinical studies have shown a beneficial effect of thiazolidinediones, synthetic PPAR-γligands, on cardiovascular disease beyond glycemic control. These results suggest that PPAR-γactivation is an important regulator in vascular inflammation and is expected to be a therapeutic target in the treatment of atherosclerotic complications. This paper reviews the recent findings of PPAR-γinvolvement in vascular inflammation and the therapeutic potential of regulating the immune system in atherosclerosis.

scholarly journals Allergen-associated molecular patterns: a new trend in modern allergology

2019 ◽  
Vol 18 (1) ◽  
pp. 76-83
Author(s):  
V. S. Sviridova ◽  
P. Yu. Isaev ◽  
V. V. Klimov ◽  
M. I. Romanova ◽  
N. S. Koshkarova
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Adaptive Immune System ◽  
Conserved Motifs ◽  
Immune Mechanisms ◽  
Adaptive Immune ◽  
Molecular Patterns

Over the last decade the role of innate immunity has been known to be crucial for the activation of adaptive immune system. The main triggers that upregulate reactions of innate immunity are small exogenous molecules with conserved motifs, molecular patterns. The article discusses a variety of possible roles of molecular patterns in the immune mechanisms, including the participation of Allergen Associated Molecular Patterns (AAMPs) in allergic processes.

Innate immune receptors in type 1 diabetes: the relationship to cell death-associated inflammation

2020 ◽  
Vol 48 (3) ◽  
pp. 1213-1225 ◽  
Author(s):  
Tae Kang Kim ◽  
Myung-Shik Lee
Keyword(s):  
Innate Immunity ◽  
Type 1 Diabetes ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Innate Immune ◽  
Therapeutic Modalities ◽  
Immune Receptors ◽  
Molecular Patterns

The importance of innate immunity in host defense and inflammatory responses has been clearly demonstrated after the discovery of innate immune receptors such as Toll-like receptors (TLRs) or Nucleotide-binding oligomerization domain-containing protein (Nod)-like receptors (NLRs). Innate immunity also plays a critical role in diverse pathological conditions including autoimmune diseases such as type 1 diabetes (T1D). In particular, the role of a variety of innate immune receptors in T1D has been demonstrated using mice with targeted disruption of such innate immune receptors. Here, we discuss recent findings showing the role of innate immunity in T1D that were obtained mostly from studies of genetic mouse models of innate immune receptors. In addition, the role of innate immune receptors involved in the pathogenesis of T1D in sensing death-associated molecular patterns (DAMPs) released from dead cells or pathogen-associated molecular patterns (PAMPs) will also be covered. Elucidation of the role of innate immune receptors in T1D and the nature of DAMPs sensed by such receptors may lead to the development of new therapeutic modalities against T1D.

scholarly journals The Role of Bacteria and Pattern Recognition Receptors in GvHD

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
E. Holler ◽  
K. Landfried ◽  
J. Meier ◽  
M. Hausmann ◽  
G. Rogler
Keyword(s):  
Innate Immunity ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Long Time ◽  
Potential Risk Factors ◽  
Pathogen Recognition Receptors ◽  
Antigen Presenting ◽  
Molecular Patterns ◽  
Gastrointestinal Decontamination

Graft-versus-Host Disease (GvHD) is the most serious complication of allogeneic stem cell transplantation (SCT) and results from an activation of donor lymphocytes by recipient antigen-presenting cells (APCs). For a long time, it has been postulated that the intestinal microflora and endotoxin exert a crucial step in this APC activation, as there is early and severe gastrointestinal damage induced by pretransplant conditioning. With the detailed description of pathogen-associated molecular patterns and pathogen recognition receptors single nucleotide polymorphisms of TLRs and especially NOD2 have been identified as potential risk factors of GvHD and transplant related complications thus further supporting the crucial role of innate immunity in SCT, related complications. Gastrointestinal decontamination and neutralization of endotoxin have been used to interfere with this early axis of activation with some success but more specific approaches of modulation of innate immunity are needed for further improvement of clinical outcome.

scholarly journals Trimethylamine N-Oxide Generated by the Gut Microbiota Is Associated with Vascular Inflammation: New Insights into Atherosclerosis

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Yarong Liu ◽  
Min Dai
Keyword(s):  
Gut Microbiota ◽  
Close Association ◽  
Vascular Inflammation ◽  
Experimental Studies ◽  
High Plasma ◽  
Chronic Inflammatory Disease ◽  
Biologically Active ◽  
Vascular Endothelial ◽  
Inflammatory Injury

Trimethylamine N-oxide (TMAO) is a biologically active molecule generated by the gut microbiota. Accumulating evidences have indicated a close association between high plasma TMAO levels and the risk of developing atherosclerosis (AS). AS is considered a chronic inflammatory disease initiated by vascular endothelial inflammatory injury. Both observational and experimental studies suggest that TMAO can cause endothelial inflammatory injury. However, a clear mechanistic link between TMAO and vascular inflammation of AS is not yet summarized. In this review, we discuss the association between TMAO and AS and focus on the potential role of TMAO in endothelial inflammatory injury. Finally, the utility of TMAO-targeted therapeutic strategies for the treatment of AS is also analyzed.

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