scholarly journals Neuroendocrine Immunoregulation in Multiple Sclerosis

2013 ◽  
Vol 2013 ◽  
pp. 1-23 ◽  
Author(s):  
Nathalie Deckx ◽  
Wai-Ping Lee ◽  
Zwi N. Berneman ◽  
Nathalie Cools
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Inflammatory Diseases ◽  
Neuroendocrine System ◽  
Extrinsic Factors ◽  
Inflammatory Stress ◽  
Factors Affecting ◽  
New Therapeutic Approaches ◽  
Messenger Molecules ◽  
Autoimmune And Inflammatory Diseases

Currently, it is generally accepted that multiple sclerosis (MS) is a complex multifactorial disease involving genetic and environmental factors affecting the autoreactive immune responses that lead to damage of myelin. In this respect, intrinsic or extrinsic factors such as emotional, psychological, traumatic, or inflammatory stress as well as a variety of other lifestyle interventions can influence the neuroendocrine system. On its turn, it has been demonstrated that the neuroendocrine system has immunomodulatory potential. Moreover, the neuroendocrine and immune systems communicate bidirectionally via shared receptors and shared messenger molecules, variously called hormones, neurotransmitters, or cytokines. Discrepancies at any level can therefore lead to changes in susceptibility and to severity of several autoimmune and inflammatory diseases. Here we provide an overview of the complex system of crosstalk between the neuroendocrine and immune system as well as reported dysfunctions involved in the pathogenesis of autoimmunity, including MS. Finally, possible strategies to intervene with the neuroendocrine-immune system for MS patient management will be discussed. Ultimately, a better understanding of the interactions between the neuroendocrine system and the immune system can open up new therapeutic approaches for the treatment of MS as well as other autoimmune diseases.

scholarly journals The Kynurenine Pathway—New Linkage between Innate and Adaptive Immunity in Autoimmune Endocrinopathies

2021 ◽  
Vol 22 (18) ◽  
pp. 9879
Author(s):  
Anna Krupa ◽  
Irina Kowalska
Keyword(s):  
Immune System ◽  
Adaptive Immunity ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Kynurenine Pathway ◽  
Wide Range ◽  
Organ Specific ◽  
Autoimmune And Inflammatory Diseases

The kynurenine pathway (KP) is highly regulated in the immune system, where it promotes immunosuppression in response to infection or inflammation. Indoleamine 2,3-dioxygenase 1 (IDO1), the main enzyme of KP, has a broad spectrum of activity on immune cells regulation, controlling the balance between stimulation and suppression of the immune system at sites of local inflammation, relevant to a wide range of autoimmune and inflammatory diseases. Various autoimmune diseases, among them endocrinopathies, have been identified to date, but despite significant progress in their diagnosis and treatment, they are still associated with significant complications, morbidity, and mortality. The precise cellular and molecular mechanisms leading to the onset and development of autoimmune disease remain poorly clarified so far. In breaking of tolerance, the cells of the innate immunity provide a decisive microenvironment that regulates immune cells’ differentiation, leading to activation of adaptive immunity. The current review provided a comprehensive presentation of the known role of IDO1 and KP activation in the regulation of the innate and adaptive arms of the immune system. Significant attention has been paid to the immunoregulatory role of IDO1 in the most prevalent, organ-specific autoimmune endocrinopathies—type 1 diabetes mellitus (T1DM) and autoimmune thyroiditis.

scholarly journals Gene expression profiling of glucocorticoid-inhibited osteoblasts

2004 ◽  
Vol 33 (1) ◽  
pp. 175-193 ◽  
Author(s):  
N Leclerc ◽  
CA Luppen ◽  
VV Ho ◽  
S Nagpal ◽  
JG Hacia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Mass ◽  
Inflammatory Diseases ◽  
Bmp Signaling ◽  
Mrna Levels ◽  
New Therapeutic Approaches ◽  
Increased Risk ◽  
Autoimmune And Inflammatory Diseases ◽  
Bmp Pathway

Glucocorticoid (GC) treatment for the management of autoimmune and inflammatory diseases is associated with decreased bone formation and increased risk for fracture. In MC3T3-E1 cell cultures, 0.1-1 microM dexamethasone (DEX) arrests development of the osteoblast phenotype when administration commences at a commitment stage around the time of confluency. To gain new insights into GC-induced osteoporosis, we performed microarray-based gene expression analysis of GC-arrested MC3T3-E1 cultures, 2.5 days after the administration of DEX. Of the >12 000 transcripts interrogated, 74 were up-regulated and 17 were down-regulated by at least 2.5-fold (P < or = 0.05). Some of these genes, such as Mmp13, Serum/GC-regulated kinase and Tieg, have previously been reported as GC-responsive. Others are shown here for the first time to respond to GCs. DEX strongly repressed Krox20/Egr2 at both the mRNA and the protein level. This is especially significant because mice lacking this transcription factor develop osteoporosis. The data also suggest that the bone morphogenetic protein (BMP) pathway, which is involved in regulating bone mass, and other pathways that influence BMP signaling, are abrogated by GCs: (i) DEX increased the mRNA levels of the BMP antagonists Follistatin and Dan; (ii) DEX increased the levels of p21 Rasgap3 and Ptpn16/MKP-1 mRNAs, negative regulators of the MAP kinase pathway; and (iii) DEX decreased Cox mRNA levels. DEX also increased thrombospondin mRNA levels, which negatively regulate bone mass in vivo, as well as the adipocytic marker Fkbp51. These and other observations disclose novel gene targets, whose regulation by GCs in osteoblasts may shed light on and provide new therapeutic approaches to osteoporosis.

scholarly journals Joint analysis reveals shared autoimmune disease associations and identifies common mechanisms

2021 ◽  
Author(s):  
Matthew R Lincoln ◽  
Noah Connally ◽  
Pierre-Paul Axisa ◽  
Christiane Gasperi ◽  
Mitja Mitrovic ◽  
...  
Keyword(s):  
Immune System ◽  
Autoimmune Disease ◽  
Fine Mapping ◽  
Inflammatory Diseases ◽  
Underlying Mechanism ◽  
Joint Analysis ◽  
Risk Alleles ◽  
Disease Associations ◽  
Autoimmune And Inflammatory Diseases ◽  
Shared Alleles

Autoimmune and inflammatory diseases are polygenic disorders of the immune system. Many genomic loci harbor risk alleles for several diseases, but the limited resolution of genetic mapping prevents deter- mining if the same allele is responsible, indicating a shared underlying mechanism. Using a collection of 129,058 cases and controls across six diseases, we show that ~40% of overlapping associations are due to the same allele. We improve fine-mapping resolution for shared alleles two-fold by combining cases and controls across diseases, allowing us to identify more eQTLs driven by the shared alleles. The patterns of sharing indicate widespread shared mechanisms, but not a single global autoimmune mecha- nism. Our approach can be applied to any set of traits, and is particularly valuable as sample collections become depleted.

scholarly journals Therapeutic Targeting of Immune Cell Autophagy in Multiple Sclerosis: Russian Roulette or Silver Bullet?

2021 ◽  
Vol 12 ◽  
Author(s):  
Guan Yang ◽  
Luc Van Kaer
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cell ◽  
Inflammatory Diseases ◽  
Chronic Inflammatory Disease ◽  
Nerve Fibers ◽  
Therapeutic Approaches ◽  
Autoimmune Encephalomyelitis ◽  
Autoimmune And Inflammatory Diseases ◽  
The Central Nervous System

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) in which the immune system damages the protective insulation surrounding nerve fibers that project from neurons. The pathological hallmark of MS is multiple areas of myelin loss accompanied by inflammation within the CNS, resulting in loss of cognitive function that ultimately leads to paralysis. Recent studies in MS have focused on autophagy, a cellular self-eating process, as a potential target for MS treatment. Here, we review the contribution of immune cell autophagy to the pathogenesis of experimental autoimmune encephalomyelitis (EAE), the prototypic animal model of MS. A better understanding of the role of autophagy in different immune cells to EAE might inform the development of novel therapeutic approaches in MS and other autoimmune and inflammatory diseases.

scholarly journals Computational design of a synthetic PD-1 agonist

2021 ◽  
Vol 118 (29) ◽  
pp. e2102164118
Author(s):  
Cassie M. Bryan ◽  
Gabriel J. Rocklin ◽  
Matthew J. Bick ◽  
Alex Ford ◽  
Sonia Majri-Morrison ◽  
...  
Keyword(s):  
Immune System ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Function ◽  
Inflammatory Diseases ◽  
Computational Design ◽  
Activated T Cells ◽  
Autoimmune And Inflammatory Diseases ◽  
Cell Death Protein

Programmed cell death protein-1 (PD-1) expressed on activated T cells inhibits T cell function and proliferation to prevent an excessive immune response, and disease can result if this delicate balance is shifted in either direction. Tumor cells often take advantage of this pathway by overexpressing the PD-1 ligand PD-L1 to evade destruction by the immune system. Alternatively, if there is a decrease in function of the PD-1 pathway, unchecked activation of the immune system and autoimmunity can result. Using a combination of computation and experiment, we designed a hyperstable 40-residue miniprotein, PD-MP1, that specifically binds murine and human PD-1 at the PD-L1 interface with a Kd of ∼100 nM. The apo crystal structure shows that the binder folds as designed with a backbone RMSD of 1.3 Å to the design model. Trimerization of PD-MP1 resulted in a PD-1 agonist that strongly inhibits murine T cell activation. This small, hyperstable PD-1 binding protein was computationally designed with an all-beta interface, and the trimeric agonist could contribute to treatments for autoimmune and inflammatory diseases.

scholarly journals Prevotella Copri and Microbiota in Rheumatoid Arthritis: Fully Convincing Evidence?

2019 ◽  
Vol 8 (11) ◽  
pp. 1837 ◽  
Author(s):  
Drago
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune System ◽  
Gut Microbiota ◽  
Inflammatory Diseases ◽  
Convincing Evidence ◽  
Immune Network ◽  
Positive Balance ◽  
Autoimmune And Inflammatory Diseases

: Gut microbiota regulates the host's immune system. Microorganisms and their compounds can co-exist peacefully with the immune system and coordinate its function and regulation. Some microbial clusters may be harmful and others helpful in the respective negative or positive balance of the immune network. These insights have revealed important mechanisms for understanding and treating autoimmune and inflammatory diseases. This Editorial aims to clarify the role of specific genus of gut microbiota, such as Prevotella, in influencing the pathogenesis of Rheumatoid Arthritis (RA).

Learned Placebo Effects in the Immune System

2014 ◽  
Vol 222 (3) ◽  
pp. 148-153 ◽  
Author(s):  
Sabine Vits ◽  
Manfred Schedlowski
Keyword(s):  
Nervous System ◽  
Immune System ◽  
Associative Learning ◽  
Placebo Response ◽  
Immunosuppressive Drug ◽  
Immune Functions ◽  
Placebo Effects ◽  
New Therapeutic Approaches ◽  
Biological Variables ◽  
Experimental Approaches

Associative learning processes are one of the major neuropsychological mechanisms steering the placebo response in different physiological systems and end organ functions. Learned placebo effects on immune functions are based on the bidirectional communication between the central nervous system (CNS) and the peripheral immune system. Based on this “hardware,” experimental evidence in animals and humans showed that humoral and cellular immune functions can be affected by behavioral conditioning processes. We will first highlight and summarize data documenting the variety of experimental approaches conditioning protocols employed, affecting different immunological functions by associative learning. Taking a well-established paradigm employing a conditioned taste aversion model in rats with the immunosuppressive drug cyclosporine A (CsA) as an unconditioned stimulus (US) as an example, we will then summarize the efferent and afferent communication pathways as well as central processes activated during a learned immunosuppression. In addition, the potential clinical relevance of learned placebo effects on the outcome of immune-related diseases has been demonstrated in a number of different clinical conditions in rodents. More importantly, the learned immunosuppression is not restricted to experimental animals but can be also induced in humans. These data so far show that (i) behavioral conditioned immunosuppression is not limited to a single event but can be reproduced over time, (ii) immunosuppression cannot be induced by mere expectation, (iii) psychological and biological variables can be identified as predictors for this learned immunosuppression. Together with experimental approaches employing a placebo-controlled dose reduction these data provide a basis for new therapeutic approaches to the treatment of diseases where a suppression of immune functions is required via modulation of nervous system-immune system communication by learned placebo effects.

Cancer stemness as a target for immunotherapy is shaped by pro-inflammatory stress.

2020 ◽  
Vol 15 ◽  
Author(s):  
Nese Unver
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Immune Cells ◽  
Tumor Recurrence ◽  
Inflammatory Factors ◽  
Cancer Stemness ◽  
Self Renewal ◽  
Inflammatory Stress ◽  
Factors Affecting

: Cancer stem cells represent a rare subpopulation of cancer cells carrying self-renewal and differentiation features in the multi-step tumorigenesis, tumor recurrence and metastasis. Pro-inflammatory stress is highly associated with cancer stemness via induction of cytokines, tumor-promoting immune cells and cancer stemness-related signaling pathways. This review summarizes the major pro-inflammatory factors affecting cancer stem cell characteristics and the critical immunotherapeutic strategies to eliminate cancer stem cells.

scholarly journals Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Anna C. Aschenbrenner ◽  
◽  
Maria Mouktaroudi ◽  
Benjamin Krämer ◽  
Marie Oestreich ◽  
...  
Keyword(s):  
Immune System ◽  
Disease Severity ◽  
Whole Blood ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Target Prediction ◽  
Data Driven ◽  
Host Responses ◽  
Drug Candidates ◽  
Drug Target Prediction

Abstract Background The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases call for a better characterization and understanding of the changes in the immune system. Methods In order to dissect COVID-19-driven immune host responses, we performed RNA-seq of whole blood cell transcriptomes and granulocyte preparations from mild and severe COVID-19 patients and analyzed the data using a combination of conventional and data-driven co-expression analysis. Additionally, publicly available data was used to show the distinction from COVID-19 to other diseases. Reverse drug target prediction was used to identify known or novel drug candidates based on finding from data-driven findings. Results Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 16 COVID-19 patients (44 samples). Comparison of COVID-19 blood transcriptomes with those of a collection of over 3100 samples derived from 12 different viral infections, inflammatory diseases, and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host. Conclusions Our study provides novel insights in the distinct molecular subgroups or phenotypes that are not simply explained by clinical parameters. We show that whole blood transcriptomes are extremely informative for COVID-19 since they capture granulocytes which are major drivers of disease severity.

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