Publications
60 results found
Sanghera C, Wong LM, Panahi M, et al., 2019, Cardiac phenotype in mouse models of systemic autoimmunity, Disease Models & Mechanisms, Vol: 12, ISSN: 1754-8403
Patients suffering from systemic autoimmune diseases are at significant risk of cardiovascular complications. This can be due to systemically increased levels of inflammation leading to accelerated atherosclerosis, or due to direct damage to the tissues and cells of the heart. Cardiac complications include an increased risk of myocardial infarction, myocarditis and dilated cardiomyopathy, valve disease, endothelial dysfunction, excessive fibrosis, and bona fide autoimmune-mediated tissue damage by autoantibodies or auto-reactive cells. There is, however, still a considerable need to better understand how to diagnose and treat cardiac complications in autoimmune patients. A range of inducible and spontaneous mouse models of systemic autoimmune diseases is available for mechanistic and therapeutic studies. For this Review, we systematically collated information on the cardiac phenotype in the most common inducible, spontaneous and engineered mouse models of systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis. We also highlight selected lesser-known models of interest to provide researchers with a decision framework to choose the most suitable model for their study of heart involvement in systemic autoimmunity.
Sattler S, Couch LS, Harding SE, 2018, Takotsubo Syndrome: Latest addition to the expanding family of immune-mediated diseases?, JACC: Basic to Translational Science, Vol: 3, Pages: 779-781, ISSN: 2452-302X
Sattler S, Ng FS, Panahi M, 2018, Immunopharmacology of post-myocardial infarction and heart failure medications, Journal of Clinical Medicine, Vol: 7, ISSN: 2077-0383
The immune system responds to acute tissue damage after myocardial infarction (MI) and orchestrates healing and recovery of the heart. However, excessive inflammation may lead to additional tissue damage and fibrosis and exacerbate subsequent functional impairment, leading to heart failure. The appreciation of the immune system as a crucial factor after MI has led to a surge of clinical trials investigating the potential benefits of immunomodulatory agents previously used in hyper-inflammatory conditions, such as autoimmune disease. While the major goal of routine post-MI pharmacotherapy is to support heart function by ensuring appropriate blood pressure and cardiac output to meet the demands of the body, several drug classes also affect a range of immunological pathways and modulate the post-MI immune response, which is crucial to take into account when designing future immunomodulatory trials. This review outlines how routine post-MI pharmacotherapy affects the immune response and may thus influence post-MI outcomes and development towards heart failure. Current key drug classes are discussed, including platelet inhibitors, statins, β-blockers, and renin–angiotensin–aldosterone inhibitors.
Panahi M, Papanikolaou A, Torabi A, et al., 2018, Immunomodulatory interventions in myocardial infarction and heart failure: a systematic review of clinical trials and meta-analysis of IL-1 inhibition, Cardiovascular Research, Vol: 114, Pages: 1445-1461, ISSN: 1755-3245
Following a myocardial infarction (MI), the immune system helps to repair ischaemic damage and restore tissue integrity, but excessive inflammation has been implicated in adverse cardiac remodelling and development towards heart failure (HF). Pre-clinical studies suggest that timely resolution of inflammation may help prevent HF development and progression. Therapeutic attempts to prevent excessive post-MI inflammation in patients have included pharmacological interventions ranging from broad immunosuppression to immunomodulatory approaches targeting specific cell types or factors with the aim to maintain beneficial aspects of the early post-MI immune response. These include the blockade of early initiators of inflammation including reactive oxygen species and complement, inhibition of mast cell degranulation and leucocyte infiltration, blockade of inflammatory cytokines, and inhibition of adaptive B and T-lymphocytes. Herein, we provide a systematic review on post-MI immunomodulation trials and a meta-analysis of studies targeting the inflammatory cytokine Interleukin-1. Despite an enormous effort into a significant number of clinical trials on a variety of targets, a striking heterogeneity in study population, timing and type of treatment, and highly variable endpoints limits the possibility for meaningful meta-analyses. To conclude, we highlight critical considerations for future studies including (i) the therapeutic window of opportunity, (ii) immunological effects of routine post-MI medication, (iii) stratification of the highly diverse post-MI patient population, (iv) the potential benefits of combining immunomodulatory with regenerative therapies, and at last (v) the potential side effects of immunotherapies.
Panahi M, Papanikolaou A, Khan H, et al., 2018, A systematic review and meta-analysis of anti-cytokine therapies targeting IL-1 and TNF- A in myocardial infarction and heart failure, European-Society-of-Cardiology Congress, Publisher: European Society of Cardiology, Pages: 599-599, ISSN: 0195-668X
Panahi M, Papanikolaou A, Khan H, et al., 2018, P2861A systematic review and meta-analysis of anti-cytokine therapies targeting IL-1 and TNF- A in myocardial infarction and heart failure, European Heart Journal, Vol: 39, ISSN: 0195-668X
Hasham M, Baxan N, Dent O, et al., 2017, Heart disease in systemic autoimmunity; an inducible mouse model to study regenerative processes and therapies under inflammatory conditions, Annual Conference of the British-Society-for-Gene-and-Cell-Therapy / Joint UK-Regenerative-Medicine-Platform Meeting, Publisher: MARY ANN LIEBERT, INC, Pages: A20-A21, ISSN: 1043-0342
, 2017, British Society for Gene and Cell Therapy Annual Conference and Joint UK Regenerative Medicine Platform Meeting Royal Welsh College of Music & Drama Cardiff, Wales, United Kingdom Wednesday April 19-Friday April 21, 2017 Conference Abstracts., Hum Gene Ther, Vol: 28, Pages: A1-A36
Sattler S, Fairchild P, Watt F, et al., 2017, The adaptive immune response to cardiac injury-the true roadblock to effective regenerative therapies?, npj Regenerative Medicine, Vol: 2, ISSN: 2057-3995
The regenerative capacity of adult human tissues and organs is limited, but recent developments have seen the advent of promising new technologies for regenerative therapy. The human heart is of particular interest for regenerative medicine, as cardiac tissue damage is repaired by the formation of rigid scar tissue, which causes inevitable structural changes and progressive functional decline leading to heart failure. Cardiac regenerative medicine aims to prevent scar formation or replace existing scars to halt or reverse adverse remodeling and therapeutic approaches include the use of biomaterials, gene therapies, delivery of growth factors and (stem) cell therapies. Regenerative therapies, however, face significant obstacles in a hostile microenvironment. While the early immune response to a myocardial infarct is essential to ensure tissue integrity and to avoid fatal cardiac rupture, excessive activation of endogenous repair mechanisms may lead to ongoing inflammation, fibrosis and sustained autoimmune-mediated tissue damage. Anti-cardiac auto-reactivity of the adaptive immune system has been suggested to be involved in structural remodeling, functional decline and the development of heart failure. It is, therefore, crucial to first understand the endogenous response to cardiac tissue damage and how to restore immune tolerance to cardiac tissue, before additional regenerative therapies can achieve their full potential.
Sattler S, 2017, The role of the immune system beyond the fight against infection, The Immunology of Cardiovascular Homeostasis and Pathology, Editors: Sattler, KennedyLydon, Publisher: Springer, Pages: 3-14, ISBN: 9783319576138
The immune system was identified as a protective factor during infectious diseases over a century ago. Current definitions and textbook information are still largely influenced by these early observations, and the immune system is commonly presented as a defence machinery. However, host defence is only one manifestation of the immune system’s overall function in the maintenance of tissue homeostasis and system integrity. In fact, the immune system is integral part of fundamental physiological processes such as development, reproduction and wound healing, and a close crosstalk between the immune system and other body systems such as metabolism, the central nervous system and the cardiovascular system is evident. Research and medical professionals in an expanding range of areas start to recognise the implications of the immune system in their respective fields.This chapter provides a brief historical perspective on how our understanding of the immune system has evolved from a defence system to an overarching surveillance machinery to maintain tissue integrity. Current perspectives on the non-defence functions of classical immune cells and factors will also be discussed
Rahman MS, Woollard K, 2017, Atherosclerosis., The Immunology of Cardiovascular Homeostasis and Pathology, Editors: Sattler, Kennedy-Lydon, Publisher: Springer, Pages: 121-144, ISBN: 978-3-319-57613-8
In this chapter, we discuss the manner through which the immune system regulates the cardiovascular system in health and disease. We define the cardiovascular system and elements of atherosclerotic disease, the main focus in this chapter. Herein we elaborate on the disease process that can result in myocardial infarction (heart attack), ischaemic stroke and peripheral arterial disease. We have discussed broadly the homeostatic mechanisms in place that help autoregulate the cardiovascular system including the vital role of cholesterol and lipid clearance as well as the role lipid homeostasis plays in cardiovascular disease in the context of atherosclerosis. We then elaborate on the role played by the immune system in this setting, namely, major players from the innate and adaptive immune system, as well as discussing in greater detail specifically the role played by monocytes and macrophages.This chapter should represent an overview of the role played by the immune system in cardiovascular homeostasis; however further reading of the references cited can expand the reader's knowledge of the detail, and we point readers to many excellent reviews which summarise individual immune systems and their role in cardiovascular disease.
Hasham MG, Baxan N, Stuckey D, et al., 2017, Systemic autoimmunity induced by Toll-like receptor 7/8 agonist Resiquimod causes myocarditis and dilated cardiomyopathy: a new model of autoimmune heart disease, Disease Models & Mechanisms, Vol: 10, Pages: 259-270, ISSN: 1754-8411
Systemic autoimmune diseases such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA) show significant heart involvement and cardiovascular morbidity, which can be due to systemically increased levels of inflammation or direct autoreactivity targeting cardiac tissue. Despite high clinical relevance, cardiac damage secondary to systemic autoimmunity lacks inducible rodent models. Here we characterize immune-mediated cardiac tissue damage in a new model of SLE induced by topical application of the TLR-7/8 agonist Resiquimod. We observe a cardiac phenotype reminiscent of autoimmune-mediated dilated cardiomyopathy, and identify auto-antibodies as major contributors to cardiac tissue damage. Resiquimod-induced heart disease is a highly relevant mouse model for mechanistic and therapeutic studies aiming to protect the heart during autoimmunity.
Delcassian D, Sattler S, Dunlop IE, 2017, T cell immunoengineering with advanced biomaterials, Integrative Biology, Vol: 9, Pages: 211-222, ISSN: 1757-9694
Recent advances in biomaterials design offer the potential to actively control immune cell activation and behaviour. Many human diseases, such as infections, cancer, and autoimmune disorders, are partly mediated by inappropriate or insufficient activation of the immune system. T cells play a central role in the host immune response to these diseases, and so constitute a promising cell type for manipulation. In vivo, T cells are stimulated by antigen presenting cells (APC), therefore to design immunoengineering biomaterials that control T cell behaviour, artificial interfaces that mimic the natural APC-T cell interaction are required. This review draws together research in the design and fabrication of such biomaterial interfaces, and highlights efforts to elucidate key parameters in T cell activation, such as substrate mechanical properties and spatial organization of receptors, illustrating how they can be manipulated by bioengineering approaches to alter T cell function.
Sattler S, Rosenthal N, 2016, The neonate versus adult mammalian immune system in cardiac repair and regeneration, BBA - Molecular Cell Research, Vol: 1863, Pages: 1813-1821, ISSN: 0167-4889
The immune system is a crucial player in tissue homeostasis and woundhealing. A sophisticated cascade of events triggered upon injury ensuresprotection from infection and initiates and orchestrates healing. While theneonatal mammal can readily regenerate damaged tissues, adult regenerativecapacity is limited to specific tissue types, and in organs such as the heart,adult wound healing results in fibrotic repair and loss of function. Growingevidence suggests that the immune system greatly influences the balancebetween regeneration and fibrotic repair. The neonate mammalian immunesystem has impaired pro-inflammatory function, is prone to T-helper type 2responses and has an immature adaptive immune system skewed towardsregulatory T cells. While these characteristics make infants susceptible toinfection and prone to allergies, it may also provide an immunologicalenvironment permissive of regeneration.In this review we will give a comprehensive overview of the immune cellsinvolved in healing and regeneration of the heart and explore differencesbetween the adult and neonate immune system that may explain differencesin regenerative ability.
Gallego Colon E, Sampson RD, Sattler S, et al., 2015, Cardiac-restricted IGF-1Ea overexpression reduces the early accumulation of inflammatory myeloid cells and mediates expression of extracellular matrix remodelling genes after myocardial infarction, Mediators of Inflammation, Vol: 2015, ISSN: 1466-1861
Strategies to limit damage and improve repair after myocardial infarct remain a major therapeutic goal in cardiology. Our previous studies have shown that constitutive expression of a locally acting insulin-like growth factor-1 Ea (IGF-1Ea) propeptide promotes functional restoration after cardiac injury associated with decreased scar formation. In the current study, we investigated the underlying molecular and cellular mechanisms behind the enhanced functional recovery. We observed improved cardiac function in mice overexpressing cardiac-specific IGF-1Ea as early as day 7 after myocardial infarction. Analysis of gene transcription revealed that supplemental IGF-1Ea regulated expression of key metalloproteinases (MMP-2 and MMP-9), their inhibitors (TIMP-1 and TIMP-2), and collagen types (Col 1α1 and Col 1α3) in the first week after injury. Infiltration of inflammatory cells, which direct the remodelling process, was also altered; in particular there was a notable reduction in inflammatory Ly6C+ monocytes at day 3 and an increase in anti-inflammatory CD206+ macrophages at day 7. Taken together, these results indicate that the IGF-1Ea transgene shifts the balance of innate immune cell populations early after infarction, favouring a reduction in inflammatory myeloid cells. This correlates with reduced extracellular matrix remodelling and changes in collagen composition that may confer enhanced scar elasticity and improved cardiac function.
Zhao H, Davies TJ, Ning J, et al., 2015, A Highly Optimized Protocol for Reprogramming Cancer Cells to Pluripotency Using Nonviral Plasmid Vectors, CELLULAR REPROGRAMMING, Vol: 17, Pages: 7-18, ISSN: 2152-4971
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- Citations: 9
Johannesson B, Sattler S, Semenova E, et al., 2014, Insulin-like growth factor-1 induces regulatory T cell-mediated suppression of allergic contact dermatitis in mice, DISEASE MODELS & MECHANISMS, Vol: 7, Pages: 977-985, ISSN: 1754-8403
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- Citations: 30
Sattler S, Ling G-S, Xu D, et al., 2014, IL-10-producing regulatory B cells induced by IL-33 (Breg(IL-33)) effectively attenuate mucosal inflammatory responses in the gut, Journal of Autoimmunity, Vol: 50, Pages: 107-122, ISSN: 0896-8411
Regulatory B cells (Breg) have attracted increasing attention for their roles in maintaining peripheral tolerance. Interleukin 33 (IL-33) is a recently identified IL-1 family member, which leads a double-life with both pro- and anti-inflammatory properties. We report here that peritoneal injection of IL-33 exacerbated inflammatory bowel disease in IL-10-deficient (IL-10−/−) mice, whereas IL-33-treated IL-10-sufficient (wild type) mice were protected from the disease induction. A phenotypically unconventional subset(s) (CD19+CD25+CD1dhiIgMhiCD5-CD23-Tim-1-) of IL-10 producing Breg-like cells (BregIL-33) was identified responsible for the protection. We demonstrated further that BregIL-33 isolated from these mice could suppress immune effector cell expansion and functions and, upon adoptive transfer, effectively blocked the development of spontaneous colitis in IL-10−/− mice. Our findings indicate an essential protective role, hence therapeutic potential, of BregIL-33 against mucosal inflammatory disorders in the gut.
Sattler S, Smits HH, Xu D, et al., 2013, The Evolutionary Role of the IL-33/ST2 System in Host Immune Defence, Arch Immunol Ther Exp (Warsz)
Interleukin (IL)-33 is a recently identified pleiotropic cytokine, which can orchestrate complex innate and adaptive immune responses in immunity and disease. It has been characterized as a cytokine of the IL-1 family and affects a wide range of immune cells by signalling through its receptor ST2L. Accumulating evidence suggests a crucial role of IL-33/ST2 in inducing and modifying host immune responses against a variety of pathogens including parasites, bacteria, viruses and fungi as well as sterile insults of both endogenous and exogenous source. In this review, we endeavour to give a comprehensive overview of the current knowledge about the role of IL-33 and its receptor ST2 in host defence against infections.
Sattler S, Hussaarts L, Ling GS, et al., 2012, Interleukin-33 mediates activation and proliferation of effector and regulatory B cells, European Congress of Immunology, Publisher: WILEY-BLACKWELL, Pages: 335-336, ISSN: 0019-2805
Huang FP, Sattler S, Ling GS, et al., 2012, An essential protective role of IL-10-producing regulatory B cells against IL-33-mediated mucosal inflammation, European Congress of Immunology, Publisher: WILEY-BLACKWELL, Pages: 77-77, ISSN: 0019-2805
Sattler S, Reiche D, Sturtzel C, et al., 2012, The Human C-Type Lectin-Like Receptor CLEC-1 is Upregulated by TGF-ß and Primarily Localized in the Endoplasmic Membrane Compartment, SCANDINAVIAN JOURNAL OF IMMUNOLOGY, Vol: 75, Pages: 282-292, ISSN: 0300-9475
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- Citations: 20
Sattler S, Ghadially H, Hofer E, 2012, Evolution of the C-type lectin-like receptor genes of the DECTIN-1 cluster in the NK gene complex, The Scientific World Journal, Vol: 2012, Pages: 1-11, ISSN: 1537-744X
Pattern recognition receptors are crucial in initiating and shaping innate and adaptive immune responses and often belong to families of structurally and evolutionarily related proteins. The human C-type lectin-like receptors encoded in the DECTIN-1 cluster within the NK gene complex contain prominent receptors with pattern recognition function, such as DECTIN-1 and LOX-1. All members of this cluster share significant homology and are considered to have arisen from subsequent gene duplications. Recent developments in sequencing and the availability of comprehensive sequence data comprising many species showed that the receptors of the DECTIN-1 cluster are not only homologous to each other but also highly conserved between species. Even in Caenorhabditis elegans, genes displaying homology to the mammalian C-type lectin-like receptors have been detected. In this paper, we conduct a comprehensive phylogenetic survey and give an up-to-date overview of the currently available data on the evolutionary emergence of the DECTIN-1 cluster genes.
Sattler S, van der Vlugt L, Hussaarts L, et al., 2012, Regulatory B cells - implications in autoimmune and allergic disorders, Recent Advances in Immunology to Target Cancer, Inflammation and Infections, Editors: Kanwar, Publisher: InTech, ISBN: 979-953-307-742-9
Huang FP, Sattler S, 2011, Regulatory T Cell Deficiency in Systemic Autoimmune Disorders – Causal Relationship and Underlying Immunological Mechanisms, Autoimmune Disorders - Pathogenetic Aspects, Editors: Mavragani, Mavragani, Publisher: InTech, Pages: 111-126, ISBN: 978-953-307-643-0
Lupus disease is very intriguing immunologically for its systemic nature and complex aetiology. Presence of autoantibodies to a diverse array of self antigens is a key feature of the lupus disorder. The broad B cell autoreactivities are known to be predominately T cell-dependent, but the mechanism underlying such a systemic loss of self tolerance is yet to be fully understood. Regulatory T cells (Treg) play many important roles in the maintenance of peripheral tolerance. Treg may exert their immunosuppressive effects on T effector cells (Teff) in an antigen-nonspecific way by the release of immunosuppressive cytokines, and possibly via their actions on dendritic cells (DC). Aberrant Treg frequencies and functions have recently been demonstrated in lupus patients, and in the animal models which develop spontaneously a lupus-like disease. These findings provided potentially therefore a plausible explanation for the systemic nature of the disease. However, there have been differences in the conclusions drawn from these various studies as to whether the lack of Treg-mediated control of auto-aggression is due to reduced Treg frequency, defective functions, or otherwise. In this chapter, we compare findings from these different studies and discuss their relevance in the context of systemic autoimmune disorders. The important issues addressed here are about the true causal relationship and underlying immunological mechanisms leading to the Treg abnormalities, as well as potential clinical implications in systemic autoimmunity. (225 words)
Sattler S, Ghadially H, Reiche D, et al., 2010, Evolutionary Development and Expression Pattern of the Myeloid Lectin-Like Receptor Gene Family Encoded Within the NK Gene Complex, SCANDINAVIAN JOURNAL OF IMMUNOLOGY, Vol: 72, Pages: 309-318, ISSN: 0300-9475
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- Citations: 11
Schweighofer B, Testori J, Sturtzel C, et al., 2009, The VEGF-induced transcriptional response comprises gene clusters at the crossroad of angiogenesis and inflammation, THROMBOSIS AND HAEMOSTASIS, Vol: 102, Pages: 544-554, ISSN: 0340-6245
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- Citations: 88
Schweighofe B, Testori J, Sturtzel C, et al., 2009, The VEGF-induced transcriptional response comprises gene clusters at the crossroad of angiogenesis and inflammation, Thromb Haemost, Vol: 3, Pages: 544-554
Resch U, Schichl YM, Sattler S, et al., 2008, XIAP regulates intracellular ROS by enhancing antioxidant gene expression, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 375, Pages: 156-161, ISSN: 0006-291X
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- Citations: 28
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