Innate Immune Mechanisms of Arterial Hypertension and Autoimmune Disease

2020 ◽  
Author(s):  
Rebecca Jung ◽  
Johannes Wild ◽  
Julia Ringen ◽  
Susanne Karbach ◽  
Philip Wenzel
Keyword(s):  
Blood Pressure ◽  
Immune System ◽  
Arterial Hypertension ◽  
Immune Cells ◽  
Vascular Dysfunction ◽  
Review Article ◽  
Innate Immune ◽  
Immune Mediated ◽  
The Central Nervous System ◽  
Relationship Of

Abstract The immune system is indispensable in the development of vascular dysfunction and hypertension. The interplay between immune cells and the vasculature, kidneys, heart, and blood pressure regulating nuclei in the central nervous system results in a complex and closely interwoven relationship of the immune system with arterial hypertension. A better understanding of this interplay is necessary for optimized and individualized antihypertensive therapy. Our review article focuses on innate cells in hypertension and to what extent they impact on development and preservation of elevated blood pressure. Moreover, we address the association of hypertension with chronic autoimmune diseases. The latter are ideally suited to learn about immune-mediated mechanisms in cardiovascular disease leading to high blood pressure.

scholarly journals A Novel Regulatory Player in the Innate Immune System: Long Non-Coding RNAs

2021 ◽  
Vol 22 (17) ◽  
pp. 9535
Author(s):  
Yuhuai Xie ◽  
Yuanyuan Wei
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Innate Immune System ◽  
Molecular Mechanisms ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Immune Mediated ◽  
Development And Differentiation ◽  
Non Coding Rnas ◽  
And Function

Long non-coding RNAs (lncRNAs) represent crucial transcriptional and post-transcriptional gene regulators during antimicrobial responses in the host innate immune system. Studies have shown that lncRNAs are expressed in a highly tissue- and cell-specific- manner and are involved in the differentiation and function of innate immune cells, as well as inflammatory and antiviral processes, through versatile molecular mechanisms. These lncRNAs function via the interactions with DNA, RNA, or protein in either cis or trans pattern, relying on their specific sequences or their transcriptions and processing. The dysregulation of lncRNA function is associated with various human non-infectious diseases, such as inflammatory bowel disease, cardiovascular diseases, and diabetes mellitus. Here, we provide an overview of the regulation and mechanisms of lncRNA function in the development and differentiation of innate immune cells, and during the activation or repression of innate immune responses. These elucidations might be beneficial for the development of therapeutic strategies targeting inflammatory and innate immune-mediated diseases.

scholarly journals Why Target Innate Immune Cells in Cancers?

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 690
Author(s):  
Mary Poupot
Keyword(s):  
Immune System ◽  
Cancer Cells ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells

The immune system is a smart way to fight cancer, with its precise targeting of cancer cells sparing healthy cells [...]

scholarly journals NCMP-05. DECODING THE IMMUNE SYSTEM RESPONSE TO LEPTOMENINGEAL METASTASIS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii124-ii124
Author(s):  
Jan Remsik ◽  
Xinran Tong ◽  
Ugur Sener ◽  
Danille Isakov ◽  
Yudan Chi ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Leptomeningeal Metastasis ◽  
System Response ◽  
Idle State ◽  
The Central Nervous System ◽  
Health And Disease ◽  
Immune System Response ◽  
Therapeutic Protocols ◽  
Brain And Spinal Cord

Abstract For decades, the central nervous system was considered to be an immune privileged organ with limited access to systemic immunity. However, the leptomeninges, the cerebrospinal fluid (CSF)-filled anatomical structure that protects the brain and spinal cord, represent a relatively immune-rich environment. Despite the presence of immune cells, complications in the CSF, such as infectious meningitis and a neurological development of cancer known as leptomeningeal metastasis, are difficult to treat and are frequently fatal. We show that immune cells entering the CSF are held in an ‘idle’ state that limits their cytotoxic arsenal and antigen presentation machinery. To understand this underappreciated neuroanatomic niche, we used unique mouse models and rare patient samples to characterize its cellular composition and critical signaling events in health and disease at a single-cell resolution. Revealing the mediators of CSF immune response will allow us to re-evaluate current therapeutic protocols and employ rational combinations with immunotherapies, therefore turning the patient’s own immune system into an active weapon against pathogens and cancer.

scholarly journals The Innate Immune System in Alzheimer’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Allal Boutajangout ◽  
Thomas Wisniewski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Innate Immune System ◽  
Late Onset ◽  
Innate Immune ◽  
Amyloid Angiopathy ◽  
Functional Variant ◽  
The Central Nervous System ◽  
Congophilic Amyloid Angiopathy

Alzheimer’s disease (AD) is the leading cause for dementia in the world. It is characterized by two biochemically distinct types of protein aggregates: amyloidβ(Aβ) peptide in the forms of parenchymal amyloid plaques and congophilic amyloid angiopathy (CAA) and aggregated tau protein in the form of intraneuronal neurofibrillary tangles (NFT). Several risk factors have been discovered that are associated with AD. The most well-known genetic risk factor for late-onset AD is apolipoprotein E4 (ApoE4) (Potter and Wisniewski (2012), and Verghese et al. (2011)). Recently, it has been reported by two groups independently that a rare functional variant (R47H) of TREM2 is associated with the late-onset risk of AD. TREM2 is expressed on myeloid cells including microglia, macrophages, and dendritic cells, as well as osteoclasts. Microglia are a major part of the innate immune system in the CNS and are also involved in stimulating adaptive immunity. Microglia express several Toll-like receptors (TLRs) and are the resident macrophages of the central nervous system (CNS). In this review, we will focus on the recent advances regarding the role of TREM2, as well as the effects of TLRs 4 and 9 on AD.

scholarly journals Adipocytes, Innate Immunity and Obesity: A Mini-Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Alecia M. Blaszczak ◽  
Anahita Jalilvand ◽  
Willa A. Hsueh
Keyword(s):  
Adipose Tissue ◽  
Immune System ◽  
Immune Cells ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Lymphoid Cells ◽  
Innate Immune Cells ◽  
Adaptive Immune

The role of adipose tissue (AT) inflammation in obesity and its multiple related-complications is a rapidly expanding area of scientific interest. Within the last 30 years, the role of the adipocyte as an endocrine and immunologic cell has been progressively established. Like the macrophage, the adipocyte is capable of linking the innate and adaptive immune system through the secretion of adipokines and cytokines; exosome release of lipids, hormones, and microRNAs; and contact interaction with other immune cells. Key innate immune cells in AT include adipocytes, macrophages, neutrophils, and innate lymphoid cells type 2 (ILC2s). The role of the innate immune system in promoting adipose tissue inflammation in obesity will be highlighted in this review. T cells and B cells also play important roles in contributing to AT inflammation and are discussed in this series in the chapter on adaptive immunity.

Abstract P145: Renal Inflammation and Injury is Associated with Increased Lymphangiogenesis in Hypertension

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Sterling C Kneedler ◽  
Lauren Phillips ◽  
Kayla R Hudson ◽  
Katharine M Beckman ◽  
Alan R Parrish ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Immune System ◽  
Immune Cells ◽  
Lymphatic Vessels ◽  
Macrophage Infiltration ◽  
Shr Rats ◽  
Renal Inflammation ◽  
Immune System Activation ◽  
System Activation ◽  
Fischer Rats

Hypertension is associated with immune system activation and inflammation. Renal infiltration of both innate and adaptive immune cells contributes to injury, dysfunction, and increased blood pressure. Activated immune cells that exit blood vessels into the interstitium then travel through lymphatic vessels to draining lymph nodes where they signal to other immune cells to increase the immune response. It is unknown how renal lymphatic vessels change in the context of hypertension, immune system activation, inflammation, and injury. We hypothesized that renal macrophage infiltration, inflammation, and injury would significantly increase lymphangiogenesis in various strains of rats. SHR rats that exhibit hypertension and renal injury (SHR-A3 strain) had significantly increased numbers of renal lymphatic vessels at 40 weeks of age compared to WKY controls (total of 3 fields of view: 52 ± 1 vs. 28 ± 1; p<0.05). This was associated with increased renal macrophage infiltration. SHR rats that exhibit hypertension but minimal renal injury (SHR-B2 strain) had significantly less renal lymphatic vessel numbers compared to WKY controls (25 ± 2 vs. 28 ± 1; p<0.05) and normal levels of macrophages. The signals for lymphangiogenesis, VEGF-C and its receptor VEGF-R3, were both increased significantly at the protein level in the kidneys of SHR-A3 rats at 18 weeks but not different in the kidneys of SHR-B2 rats compared to WKY controls. To test whether the increased lymphangiogensis is due to hypertension and/or renal inflammation and injury, we obtained kidneys from Fischer 344 rats that exhibit normal blood pressure but develop renal inflammation and injury as they age. Compared to kidneys from control 4-month old Fischer rats, kidneys from 20-month and 24-month old Fischer rats had significantly increased numbers of lymphatic vessels (32 ± 3 vs. 74 ± 1 vs. 110 ± 6, respectively; p<0.05) and this was also associated with increased macrophage infiltration. Protein levels of VEGF-C and VEGF-R3 were increased significantly in 20-month old Fischer rats compared to 4-month old controls. These data together demonstrate that renal immune cell infiltration, inflammation, and injury increases lymphangiogenesis.

Abstract 343: Vascular Inflammation in Two Rat Models of Arterial Hypertension is Promoted by Coagulation FXI

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Jeremy Lagrange ◽  
Sabine Kossmann ◽  
Andreas Daiber ◽  
Matthias Oelze ◽  
Brett Monia ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Arterial Hypertension ◽  
Feedback Loop ◽  
Thrombin Generation ◽  
Vascular Reactivity ◽  
Platelet Rich Plasma ◽  
Vascular Dysfunction ◽  
Vascular Inflammation ◽  
Critical Role ◽  
Experimental Hypertension

Backgroud: Interactions of platelets, leukocytes and the vessel wall play pivotal roles in activating coagulation and precipitating thrombosis. We were recently able to uncover an angiotensin II (ATII) driven factor XI (FXI)-thrombin amplification loop leading to vascular injury in experimental hypertension in mice. Objective: We wanted was to explore the role of thrombin-FXI feedback loop in different models of arterial hypertension in rats. Methods: ATII treated wistar rats (1mg·kg -1 ·d -1 for 7 days using osmotic minipumps) and 5/6 nephrectomized were used for this study. During 2 weeks rats were treated with a FXI antisense oligonucleotide (ASO) (1 week after nephrectomy or 2 weeks before ATII pump implantation, respectively). Blood pressure was recorded with tail cuff measurement. Fluorescence oxidative microtopography was used to evaluate vascular ROS production. Vascular reactivity was assessed in isolated aortic segment. Calibrated automated thrombography was used to measure thrombin generation. Results: In ATII infused rats as well as 5/6 nephrectomized rats vascular dysfunction related to hypertension was attenuated when rats were treated with FXI ASO. Hypertension induced VCAM-1 expression was normalize with inhibition of FXI. ROS formation was normalized in ATII infused rats as well as 5/6 nephrectomized treated with FXI ASO. Thrombin generation in platelet rich plasma from 5/6 nephrectomized rats was completely abolished when FXI was inhibited. Finally the overall blood pressure increase was abrogated by FXI ASO treatment in 5/6 nephrectomized rats. Conclusion: FXI plays a critical role in a FXI-thrombin feedback loop in hypertension. This pathway is relevant in mice and rats and we were able to very recently obtain the first conclusive results in humans. FXI could be a novel therapeutic target to interrupt this heterotypic cellular coagulation-inflammatory circuit.

scholarly journals Role of 5-HT7 receptors in the immune system in health and disease

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
Alejandro Quintero-Villegas ◽  
Sergio Iván Valdés-Ferrer
Keyword(s):  
Central Nervous System ◽  
Immune Response ◽  
Nervous System ◽  
Immune System ◽  
Blood Platelets ◽  
Pain Tolerance ◽  
Immune Mediated ◽  
The Central Nervous System ◽  
Health And Disease

AbstractIn mammalians, serotonin (5-HT) has critical roles in the central nervous system (CNS), including mood stability, pain tolerance, or sleep patterns. However, the vast majority of serotonin is produced by intestinal enterochromaffin cells of the gastrointestinal tract and circulating blood platelets, also acting outside of the CNS. Serotonin effects are mediated through its interaction with 5-HT receptors (5-HTRs), a superfamily with a repertoire of at least fourteen well-characterized members. 5-HT7 receptors are the last 5-HTR member to be identified, with well-defined functions in the nervous, gastrointestinal, and vascular systems. The effects of serotonin on the immune response are less well understood. Mast cells are known to produce serotonin, while T cells, dendritic cells, monocytes, macrophages and microglia express 5-HT7 receptor. Here, we review the known roles of 5-HT7 receptors in the immune system, as well as their potential therapeutic implication in inflammatory and immune-mediated disorders.

Evidence for B cell maturation but not trained immunity in uninfected infants exposed to hepatitis C virus

Gut ◽  
2020 ◽  
Vol 69 (12) ◽  
pp. 2203-2213 ◽  
Author(s):  
Anton Lutckii ◽  
Benedikt Strunz ◽  
Anton Zhirkov ◽  
Olga Filipovich ◽  
Elena Rukoiatkina ◽  
...  
Keyword(s):  
Immune System ◽  
B Cells ◽  
B Cell ◽  
Immune Cells ◽  
Immune Cell ◽  
Innate Immune ◽  
Cell Maturation ◽  
Innate Immune Cells ◽  
B Cell Maturation ◽  
Exposed Uninfected

ObjectivesVertical transmission of hepatitis C virus (HCV) is rare compared with other chronic viral infections, despite that newborns have an immature, and possibly more susceptible, immune system. It further remains unclear to what extent prenatal and perinatal exposure to HCV affects immune system development in neonates.DesignTo address this, we studied B cells, innate immune cells and soluble factors in a cohort of 62 children that were either unexposed, exposed uninfected or infected with HCV. Forty of these infants were followed longitudinally from birth up until 18 months of age.ResultsAs expected, evidence for B cell maturation was observed with increased age in children, whereas few age-related changes were noticed among innate immune cells. HCV-infected children had a high frequency of HCV-specific IgG-secreting B cells. Such a response was also detected in some exposed but uninfected children but not in uninfected controls. Consistent with this, both HCV-exposed uninfected and HCV-infected infants had evidence of early B cell immune maturation with an increased proportion of IgA-positive plasma cells and upregulated CD40 expression. In contrast, actual HCV viraemia, but not mere exposure, led to alterations within myeloid immune cell populations, natural killer (NK) cells and a distinct soluble factor profile with increased levels of inflammatory cytokines and chemokines.ConclusionOur data reveal that exposure to, and infection with, HCV causes disparate effects on adaptive B cells and innate immune cell such as myeloid cells and NK cells in infants.

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