The Experts below are selected from a list of 28575 Experts worldwide ranked by ideXlab platform
Gabriel A Rabinovich - One of the best experts on this subject based on the ideXlab platform.
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Immunoglycobiology: An Overview
Glycoscience: Biology and Medicine, 2021Co-Authors: Ada G. Blidner, Juan M Ilarregui, Gabriel A RabinovichAbstract:Although originally proposed as functional tuners capable of influencing signaling thresholds of Immune Cells, emerging evidence indicates a more central and hierarchical role of glycans and glycan-binding proteins as stimulators or inhibitors of innate and adaptive immunity. An increasing number of studies reveal the relevance of glycan-containing information in host-pathogen recognition and the control of Immune Cell Homeostasis, inflammation, and tumor immunity. In this chapter, we summarize general concepts of glycoimmunologyGlycoimmunology and illustrate selected examples of the contribution of glycans and glycan-binding proteins (C-type lectins, siglecs, and galectins) to innate and adaptive Immune responses in physiologic and pathologic settings.
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Galectin-1 as an Emerging Mediator of Cardiovascular Inflammation: Mechanisms and Therapeutic Opportunities
Mediators of inflammation, 2018Co-Authors: Ignacio M. Seropian, Germán E. González, Sebastian Matias Maller, Daniel Berrocal, Antonio Abbate, Gabriel A RabinovichAbstract:Galectin-1 (Gal-1), an evolutionarily conserved β-galactoside-binding lectin, controls Immune Cell Homeostasis and tempers acute and chronic inflammation by blunting proinflammatory cytokine synthesis, engaging T-Cell apoptotic programs, promoting expansion of T regulatory (Treg) Cells, and deactivating antigen-presenting Cells. In addition, this lectin promotes angiogenesis by co-opting the vascular endothelial growth factor receptor (VEGFR) 2 signaling pathway. Since a coordinated network of immunomodulatory and proangiogenic mediators controls cardiac Homeostasis, this lectin has been proposed to play a key hierarchical role in cardiac pathophysiology via glycan-dependent regulation of inflammatory responses. Here, we discuss the emerging roles of Gal-1 in cardiovascular diseases including acute myocardial infarction, heart failure, Chagas cardiomyopathy, pulmonary hypertension, and ischemic stroke, highlighting underlying anti-inflammatory mechanisms and therapeutic opportunities. Whereas Gal-1 administration emerges as a potential novel treatment option in acute myocardial infarction and ischemic stroke, Gal-1 blockade may contribute to attenuate pulmonary arterial hypertension.
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Untangling Galectin-Driven Regulatory Circuits in AutoImmune Inflammation
Trends in molecular medicine, 2018Co-Authors: Marta A. Toscano, Gabriel A Rabinovich, Verónica Candela Martínez Allo, Anabela María Cutine, Karina MariñoAbstract:Although progress has been made in understanding the mechanisms implicated in the pathogenesis of autoImmune inflammation, studies aimed at identifying the mediators of these pathways will be necessary to develop more selective therapies. Galectins, a family of glycan-binding proteins, play central roles in Immune Cell Homeostasis. Whereas some members of this family trigger regulatory programs that promote resolution of inflammation, others contribute to perpetuate autoImmune processes. We discuss the roles of endogenous galectins and their specific glycosylated ligands in shaping autoImmune responses by fueling, extinguishing, or rewiring Immune circuits. Understanding the relevance of galectin–glycan interactions in autoImmune inflammation could help to uncover novel pathways of tolerance breakdown, define molecular signatures for patient stratification and therapy responses, and open new avenues for Immune intervention.
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Galectins: emerging regulatory checkpoints linking tumor immunity and angiogenesis
Current opinion in immunology, 2017Co-Authors: Santiago P. Méndez-huergo, Ada G. Blidner, Gabriel A RabinovichAbstract:Immune checkpoints, a plethora of inhibitory pathways aimed at maintaining Immune Cell Homeostasis, may be co-opted by cancer Cells to evade Immune destruction. Therapies targeting Immune checkpoints have reached a momentum yielding significant clinical benefits in patients with various malignancies by unleashing anti-tumor immunity. Galectins, a family of glycan-binding proteins, have emerged as novel regulatory checkpoints that promote Immune evasive programs by inducing T-Cell exhaustion, limiting T-Cell survival, favoring expansion of regulatory T Cells, de-activating natural killer Cells and polarizing myeloid Cells toward an immunosuppressive phenotype. Concomitantly, galectins can trigger vascular signaling programs, serving as bifunctional messengers that couple tumor immunity and angiogenesis. Thus, targeting galectin–glycan interactions may halt tumor progression by simultaneously augmenting antitumor immunity and suppressing aberrant angiogenesis.
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Re-wiring regulatory Cell networks in immunity by galectin–glycan interactions
FEBS letters, 2015Co-Authors: Ada G. Blidner, Santiago P. Méndez-huergo, Alejandro J. Cagnoni, Gabriel A RabinovichAbstract:Programs that control Immune Cell Homeostasis are orchestrated through the coordinated action of a number of regulatory Cell populations, including regulatory T Cells, regulatory B Cells, myeloid-derived suppressor Cells, alternatively-activated macrophages and tolerogenic dendritic Cells. These regulatory Cell populations can prevent harmful inflammation following completion of protective responses and thwart the development of autoImmune pathology. However, they also have a detrimental role in cancer by favoring escape from Immune surveillance. One of the hallmarks of regulatory Cells is their remarkable plasticity as they can be positively or negatively modulated by a plethora of cytokines, growth factors and co-stimulatory signals that tailor their differentiation, stability and survival. Here we focus on the emerging roles of galectins, a family of highly conserved glycan-binding proteins in regulating the fate and function of regulatory Immune Cell populations, both of lymphoid and myeloid origins. Given the broad distribution of circulating and tissue-specific galectins, understanding the relevance of lectin–glycan interactions in shaping regulatory Cell compartments will contribute to the design of novel therapeutic strategies aimed at modulating their function in a broad range of immunological disorders.
David Artis - One of the best experts on this subject based on the ideXlab platform.
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stromal Cells maintain Immune Cell Homeostasis in adipose tissue via production of interleukin 33
Science immunology, 2019Co-Authors: Tanel Mahlakoiv, Annelaure Flamar, L K Johnston, Saya Moriyama, Gregory Garbes Putzel, Paul J Bryce, David ArtisAbstract:Obesity is driven by chronic low-grade inflammation resulting from dysregulated Immune Cell accumulation and function in white adipose tissue (WAT). Interleukin-33 (IL-33) is a key cytokine that controls innate and adaptive Immune Cell activity and Immune Homeostasis in WAT, although the sources of IL-33 have remained controversial. Here, we show that WAT-resident mesenchyme-derived stromal Cells are the dominant producers of IL-33. Adipose stem and progenitor Cells (ASPCs) produced IL-33 in all WAT depots, whereas mesothelial Cells served as an additional source of IL-33 in visceral WAT. ASPC-derived IL-33 promoted a regulatory circuit that maintained an Immune tone in WAT via the induction of group 2 innate lymphoid Cell-derived type 2 cytokines and maintenance of eosinophils, whereas mesothelial IL-33 also acted as an alarmin by inducing peritoneal Immune response upon infection. Together, these data reveal a previously unrecognized regulatory network between tissue-resident progenitor Cells and innate lymphoid Cells that maintains Immune Homeostasis in adipose tissue.
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Anatomical localization of commensal bacteria in Immune Cell Homeostasis and disease
Immunological reviews, 2014Co-Authors: Thomas C. Fung, David Artis, Gregory F. SonnenbergAbstract:Summary The mammalian gastrointestinal (GI) tract is colonized by trillions of beneficial commensal bacteria that are essential for promoting normal intestinal physiology. While the majority of commensal bacteria are found in the intestinal lumen, many species have also adapted to colonize different anatomical locations in the intestine, including the surface of intestinal epithelial Cells (IECs) and the interior of gut-associated lymphoid tissues. These distinct tissue localization patterns permit unique interactions with the mammalian Immune system and collectively influence intestinal Immune Cell Homeostasis. Conversely, dysregulated localization of commensal bacteria can lead to inappropriate activation of the Immune system and is associated with numerous chronic infectious, inflammatory, and metabolic diseases. Therefore, regulatory mechanisms that control proper anatomical containment of commensal bacteria are essential to maintain tissue Homeostasis and limit pathology. In this review, we propose that commensal bacteria associated with the mammalian GI tract can be anatomically defined as (i) luminal, (ii) epithelial-associated, or (iii) lymphoid tissue-resident, and we discuss the role and regulation of these microbial populations in health and disease.
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intestinal epithelial Cells regulators of barrier function and Immune Homeostasis
Nature Reviews Immunology, 2014Co-Authors: Lance W Peterso, David ArtisAbstract:The abundance of innate and adaptive Immune Cells that reside together with trillions of beneficial commensal microorganisms in the mammalian gastrointestinal tract requires barrier and regulatory mechanisms that conserve host-microbial interactions and tissue Homeostasis. This Homeostasis depends on the diverse functions of intestinal epithelial Cells (IECs), which include the physical segregation of commensal bacteria and the integration of microbial signals. Hence, IECs are crucial mediators of intestinal Homeostasis that enable the establishment of an immunological environment permissive to colonization by commensal bacteria. In this Review, we provide a comprehensive overview of how IECs maintain host-commensal microbial relationships and Immune Cell Homeostasis in the intestine.
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Intestinal Bacteria and the Regulation of Immune Cell Homeostasis
Annual Review of Immunology, 2010Co-Authors: David A Hill, David ArtisAbstract:The human intestine is colonized by an estimated 100 trillion bacteria. Some of these bacteria are essential for normal physiology, whereas others have been implicated in the pathogenesis of multiple inflammatory diseases including IBD and asthma. This review examines the influence of signals from intestinal bacteria on the Homeostasis of the mammalian Immune system in the context of health and disease. We review the bacterial composition of the mammalian intestine, known bacterial-derived immunoregulatory molecules, and the mammalian innate Immune receptors that recognize them. We discuss the influence of bacterial-derived signals on Immune Cell function and the mechanisms by which these signals modulate the development and progression of inflammatory disease. We conclude with an examination of successes and future challenges in using bacterial communities or their products in the prevention or treatment of human disease.
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Metagenomic analyses reveal antibiotic-induced temporal and spatial changes in intestinal microbiota with associated alterations in Immune Cell Homeostasis
Mucosal immunology, 2009Co-Authors: David A Hill, Michael C. Abt, Christian Hoffmann, Dmytro Kobuley, Thomas J. Kirn, Frederic D. Bushman, David ArtisAbstract:Despite widespread use of antibiotics, few studies have measured their effects on the burden or diversity of bacteria in the mammalian intestine. We developed an oral antibiotic treatment protocol and characterized its effects on murine intestinal bacterial communities and Immune Cell Homeostasis. Antibiotic administration resulted in a 10-fold reduction in the amount of intestinal bacteria present and sequencing of 16S rDNA segments revealed significant temporal and spatial effects on luminal and mucosal-associated communities including reductions in luminal Firmicutes and mucosal-associated Lactobacillus species, and persistence of bacteria belonging to the Bacteroidetes and Proteobacteria phyla. Concurrently, antibiotic administration resulted in reduced RELM beta production, and reduced production of interferon-gamma and interleukin-17A by mucosal CD4(+) T lymphocytes. This comprehensive temporal and spatial metagenomic analyses will provide a resource and framework to test the influence of bacterial communities in murine models of human disease.
Irina Kareva - One of the best experts on this subject based on the ideXlab platform.
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metabolism and gut microbiota in cancer immunoediting cd8 treg ratios Immune Cell Homeostasis and cancer immuno therapy concise review
Stem Cells, 2019Co-Authors: Irina KarevaAbstract:The concept of immunoediting, a process whereby the Immune system eliminates immunogenic cancer Cell clones, allowing the remaining Cells to progress and form a tumor, has evolved with growing appreciation of the importance of cancer ecology on tumor progression. As cancer Cells grow and modify their environment, they create spatial and nutrient constraints that may affect not only Immune Cell function but also differentiation, tipping the balance between cytotoxic and regulatory immunity to facilitate tumor growth. Here, we review how immunometabolism may contribute to cancer escape from the Immune system, as well as highlight an emerging role of gut microbiota, its effects on the Immune system and on response to immunotherapy. We conclude with a discussion of how these pieces can be integrated to devise better combination therapies and highlight the role of computational approaches as a potential tool to aid in combination therapy design. Stem Cells 2019;37:1273-1280.
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Metabolism and Gut Microbiota in Cancer Immunoediting, CD8/Treg Ratios, Immune Cell Homeostasis, and Cancer (Immuno)Therapy: Concise Review.
Stem cells (Dayton Ohio), 2019Co-Authors: Irina KarevaAbstract:The concept of immunoediting, a process whereby the Immune system eliminates immunogenic cancer Cell clones, allowing the remaining Cells to progress and form a tumor, has evolved with growing appreciation of the importance of cancer ecology on tumor progression. As cancer Cells grow and modify their environment, they create spatial and nutrient constraints that may affect not only Immune Cell function but also differentiation, tipping the balance between cytotoxic and regulatory immunity to facilitate tumor growth. Here, we review how immunometabolism may contribute to cancer escape from the Immune system, as well as highlight an emerging role of gut microbiota, its effects on the Immune system and on response to immunotherapy. We conclude with a discussion of how these pieces can be integrated to devise better combination therapies and highlight the role of computational approaches as a potential tool to aid in combination therapy design. Stem Cells 2019;37:1273-1280.
Shannon J. Turley - One of the best experts on this subject based on the ideXlab platform.
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Stromal infrastructure of the lymph node and coordination of immunity
Trends in immunology, 2014Co-Authors: Jonathan E. Chang, Shannon J. TurleyAbstract:The initiation of adaptive Immune responses depends upon the careful maneuvering of lymphocytes and antigen into and within strategically placed lymph nodes (LNs). Non-hematopoietic stromal Cells form the Cellular infrastructure that directs this process. Once regarded as merely structural features of lymphoid tissues, these Cells are now appreciated as essential regulators of Immune Cell trafficking, fluid flow, and LN Homeostasis. Recent advances in the identification and in vivo targeting of specific stromal populations have resulted in striking new insights to the function of stromal Cells and reveal a level of complexity previously unrealized. We discuss here recent discoveries that highlight the pivotal role that stromal Cells play in orchestrating Immune Cell Homeostasis and adaptive immunity.
Ada G. Blidner - One of the best experts on this subject based on the ideXlab platform.
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Immunoglycobiology: An Overview
Glycoscience: Biology and Medicine, 2021Co-Authors: Ada G. Blidner, Juan M Ilarregui, Gabriel A RabinovichAbstract:Although originally proposed as functional tuners capable of influencing signaling thresholds of Immune Cells, emerging evidence indicates a more central and hierarchical role of glycans and glycan-binding proteins as stimulators or inhibitors of innate and adaptive immunity. An increasing number of studies reveal the relevance of glycan-containing information in host-pathogen recognition and the control of Immune Cell Homeostasis, inflammation, and tumor immunity. In this chapter, we summarize general concepts of glycoimmunologyGlycoimmunology and illustrate selected examples of the contribution of glycans and glycan-binding proteins (C-type lectins, siglecs, and galectins) to innate and adaptive Immune responses in physiologic and pathologic settings.
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Galectins: emerging regulatory checkpoints linking tumor immunity and angiogenesis
Current opinion in immunology, 2017Co-Authors: Santiago P. Méndez-huergo, Ada G. Blidner, Gabriel A RabinovichAbstract:Immune checkpoints, a plethora of inhibitory pathways aimed at maintaining Immune Cell Homeostasis, may be co-opted by cancer Cells to evade Immune destruction. Therapies targeting Immune checkpoints have reached a momentum yielding significant clinical benefits in patients with various malignancies by unleashing anti-tumor immunity. Galectins, a family of glycan-binding proteins, have emerged as novel regulatory checkpoints that promote Immune evasive programs by inducing T-Cell exhaustion, limiting T-Cell survival, favoring expansion of regulatory T Cells, de-activating natural killer Cells and polarizing myeloid Cells toward an immunosuppressive phenotype. Concomitantly, galectins can trigger vascular signaling programs, serving as bifunctional messengers that couple tumor immunity and angiogenesis. Thus, targeting galectin–glycan interactions may halt tumor progression by simultaneously augmenting antitumor immunity and suppressing aberrant angiogenesis.
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Re-wiring regulatory Cell networks in immunity by galectin–glycan interactions
FEBS letters, 2015Co-Authors: Ada G. Blidner, Santiago P. Méndez-huergo, Alejandro J. Cagnoni, Gabriel A RabinovichAbstract:Programs that control Immune Cell Homeostasis are orchestrated through the coordinated action of a number of regulatory Cell populations, including regulatory T Cells, regulatory B Cells, myeloid-derived suppressor Cells, alternatively-activated macrophages and tolerogenic dendritic Cells. These regulatory Cell populations can prevent harmful inflammation following completion of protective responses and thwart the development of autoImmune pathology. However, they also have a detrimental role in cancer by favoring escape from Immune surveillance. One of the hallmarks of regulatory Cells is their remarkable plasticity as they can be positively or negatively modulated by a plethora of cytokines, growth factors and co-stimulatory signals that tailor their differentiation, stability and survival. Here we focus on the emerging roles of galectins, a family of highly conserved glycan-binding proteins in regulating the fate and function of regulatory Immune Cell populations, both of lymphoid and myeloid origins. Given the broad distribution of circulating and tissue-specific galectins, understanding the relevance of lectin–glycan interactions in shaping regulatory Cell compartments will contribute to the design of novel therapeutic strategies aimed at modulating their function in a broad range of immunological disorders.
