scholarly journals Age-related Immune-Stromal Networks Inhibit Response to Regenerative Immunotherapies

2021 ◽  
Author(s):  
Jin Han ◽  
Christopher Cherry ◽  
Anna Ruta ◽  
David R. Maestas ◽  
Joscelyn C. Mejias ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Neutralizing Antibodies ◽  
Tissue Repair ◽  
Therapeutic Response ◽  
Tissue Injury ◽  
Inflammatory Diseases ◽  
Communication Analysis ◽  
Age Related ◽  
Immunological Changes ◽  
Immune Changes

Aging is associated with immunological changes that compromise response to infections and vaccines, exacerbate inflammatory diseases and could potentially mitigate tissue repair. Indeed, regenerative medicine strategies designed to promote tissue repair are now focusing on the immune system as a therapeutic target due to its role in response to tissue damage and regulation of tissue repair. However, age-related immune changes to the response to damage and the resulting impact on repair remains unknown. Here, we characterized age-related immunological changes that inhibit tissue repair and therapeutic response to a clinical regenerative biological scaffold derived from extracellular matrix (ECM). We found that aging reduced the response of interleukin (IL)4 producing eosinophils and CD4 T cells in a volumetric muscle injury treated with ECM leading to reduced repair and increased fibrosis. Single cell RNA sequencing and cell-cell communication analysis via transcription factor (TF) activation revealed diminished interactions between immune and stromal modules in aging animals. Validation of the age-specific TFs and predicated protein interactions in the tissue and draining lymph nodes found multiple genes activated in old animals only after injury that were primarily related to IL17 signaling. Local inhibition of age-related type 3 immune activation using IL17-neutralizing antibodies restored therapeutic response to ECM and promoted muscle repair in older animals through increased recruitment of IL4 producing immune cells and regenerating muscle fibers. Altogether, innate and adaptive immune changes that occur with aging, in combination with dysregulated stromal communication, contribute to an impaired response to tissue injury which can be overcome with combination immunotherapy.

Annexin A1 and resolution of inflammation: tissue repairing properties and signalling signature

2016 ◽  
Vol 397 (10) ◽  
pp. 981-993 ◽  
Author(s):  
Thomas Gobbetti ◽  
Sadani N. Cooray
Keyword(s):  
Tissue Repair ◽  
Tissue Injury ◽  
Inflammatory Diseases ◽  
Molecular Targets ◽  
Biological Properties ◽  
Innate Immune ◽  
Therapeutic Effects ◽  
Annexin A1 ◽  
Persistent Inflammation ◽  
Tissue Healing

AbstractInflammation is essential to protect the host from exogenous and endogenous dangers that ultimately lead to tissue injury. The consequent tissue repair is intimately associated with the fate of the inflammatory response. Restoration of tissue homeostasis is achieved through a balance between pro-inflammatory and anti-inflammatory/pro-resolving mediators. In chronic inflammatory diseases such balance is compromised, resulting in persistent inflammation and impaired healing. During the last two decades the glucocorticoid-regulated protein Annexin A1 (AnxA1) has emerged as a potent pro-resolving mediator acting on several facets of the innate immune system. Here, we review the therapeutic effects of AnxA1 on tissue healing and repairing together with the molecular targets responsible for these complex biological properties.

Emerging Promise of Immunotherapy for Alzheimer’s Disease: A New Hope for the Development of Alzheimer’s Vaccine

2020 ◽  
Vol 20 (13) ◽  
pp. 1214-1234 ◽  
Author(s):  
Md. Tanvir Kabir ◽  
Md. Sahab Uddin ◽  
Bijo Mathew ◽  
Pankoj Kumar Das ◽  
Asma Perveen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune Response ◽  
Neutralizing Antibodies ◽  
Neurodegenerative Disorder ◽  
Symptomatic Relief ◽  
Aβ Oligomers ◽  
Th2 Immune Response ◽  
Age Related ◽  
Anti Inflammatory

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the characteristics of this devastating disorder include the progressive and disabling deficits in the cognitive functions including reasoning, attention, judgment, comprehension, memory, and language. Objective: In this article, we have focused on the recent progress that has been achieved in the development of an effective AD vaccine. Summary: Currently, available treatment options of AD are limited to deliver short-term symptomatic relief only. A number of strategies targeting amyloid-beta (Aβ) have been developed in order to treat or prevent AD. In order to exert an effective immune response, an AD vaccine should contain adjuvants that can induce an effective anti-inflammatory T helper 2 (Th2) immune response. AD vaccines should also possess the immunogens which have the capacity to stimulate a protective immune response against various cytotoxic Aβ conformers. The induction of an effective vaccine’s immune response would necessitate the parallel delivery of immunogen to dendritic cells (DCs) and their priming to stimulate a Th2-polarized response. The aforesaid immune response is likely to mediate the generation of neutralizing antibodies against the neurotoxic Aβ oligomers (AβOs) and also anti-inflammatory cytokines, thus preventing the AD-related inflammation. Conclusion: Since there is an age-related decline in the immune functions, therefore vaccines are more likely to prevent AD instead of providing treatment. AD vaccines might be an effective and convenient approach to avoid the treatment-related huge expense.

scholarly journals Future Perspectives of Therapeutic, Diagnostic and Prognostic Aptamers in Eye Pathological Angiogenesis

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1455
Author(s):  
Emilio Iturriaga-Goyon ◽  
Beatriz Buentello-Volante ◽  
Fátima Sofía Magaña-Guerrero ◽  
Yonathan Garfias
Keyword(s):  
Clinical Trials ◽  
Macular Degeneration ◽  
Small Molecules ◽  
Inflammatory Diseases ◽  
Age Related Macular Degeneration ◽  
Future Perspectives ◽  
Whole Cells ◽  
Pathological Angiogenesis ◽  
Age Related ◽  
Viral Particles

Aptamers are single-stranded DNA or RNA oligonucleotides that are currently used in clinical trials due to their selectivity and specificity to bind small molecules such as proteins, peptides, viral particles, vitamins, metal ions and even whole cells. Aptamers are highly specific to their targets, they are smaller than antibodies and fragment antibodies, they can be easily conjugated to multiple surfaces and ions and controllable post-production modifications can be performed. Aptamers have been therapeutically used for age-related macular degeneration, cancer, thrombosis and inflammatory diseases. The aim of this review is to highlight the therapeutic, diagnostic and prognostic possibilities associated with aptamers, focusing on eye pathological angiogenesis.

scholarly journals Carotenoids in the Management of Glaucoma: A Systematic Review of the Evidence

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1949
Author(s):  
Drake W. Lem ◽  
Dennis L. Gierhart ◽  
Pinakin Gunvant Davey
Keyword(s):  
Systematic Review ◽  
Tissue Injury ◽  
Open Angle Glaucoma ◽  
Synaptic Activity ◽  
Antioxidant Defenses ◽  
Cochrane Library ◽  
Retinal Ganglion ◽  
Age Related ◽  
Retinal Ganglion Cell Survival ◽  
Oxidative Insult

Primary open-angle glaucoma (POAG) remains a leading cause of irreversible blindness globally. Recent evidence further substantiates sustained oxidative stress, and compromised antioxidant defenses are key drivers in the onset of glaucomatous neurodegeneration. Overwhelming oxidative injury is likely attributed to compounding mitochondrial dysfunction that worsens with age-related processes, causing aberrant formation of free radical species. Thus, a compromised systemic antioxidant capacity exacerbates further oxidative insult in glaucoma, leading to apoptosis, neuroinflammation, and subsequent tissue injury. The purpose of this systematic review is to investigate the neuroprotective benefits of the macular carotenoids lutein, zeaxanthin, and meso-zeaxanthin on glaucomatous neurodegeneration for the purpose of adjunctive nutraceutical treatment in glaucoma. A comprehensive literature search was conducted in three databases (PubMed, Cochrane Library, and Web of Science) and 20 records were identified for screening. Lutein demonstrated enhanced neuroprotection on retinal ganglion cell survival and preserved synaptic activity. In clinical studies, a protective trend was seen with greater dietary consumption of carotenoids and risk of glaucoma, while greater carotenoid levels in macular pigment were largely associated with improved visual performance in glaucomatous eyes. The data suggest that carotenoid vitamin therapy exerts synergic neuroprotective benefits and has the capacity to serve adjunctive therapy in the management of glaucoma.

scholarly journals Polyphenol Supplementation Reverses Age-Related Changes in Microglial Signaling Cascades

2021 ◽  
Vol 22 (12) ◽  
pp. 6373
Author(s):  
Ahmad Jalloh ◽  
Antwoine Flowers ◽  
Charles Hudson ◽  
Dale Chaput ◽  
Jennifer Guergues ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Control Diet ◽  
Bioinformatic Analysis ◽  
Diet Group ◽  
Differentially Expressed ◽  
Signaling Cascades ◽  
Complex Nature ◽  
Differentially Expressed Proteins ◽  
Ms Analysis ◽  
Age Related

Microglial activity in the aging neuroimmune system is a central player in aging-related dysfunction. Aging alters microglial function via shifts in protein signaling cascades. These shifts can propagate neurodegenerative pathology. Therapeutics require a multifaceted approach to understand and address the stochastic nature of this process. Polyphenols offer one such means of rectifying age-related decline. Our group used mass spectrometry (MS) analysis to explicate the complex nature of these aging microglial pathways. In our first experiment, we compared primary microglia isolated from young and aged rats and identified 197 significantly differentially expressed proteins between these groups. Then, we performed bioinformatic analysis to explore differences in canonical signaling cascades related to microglial homeostasis and function with age. In a second experiment, we investigated changes to these pathways in aged animals after 30-day dietary supplementation with NT-020, which is a blend of polyphenols. We identified 144 differentially expressed proteins between the NT-020 group and the control diet group via MS analysis. Bioinformatic analysis predicted an NT-020 driven reversal in the upregulation of age-related canonical pathways that control inflammation, cellular metabolism, and proteostasis. Our results highlight salient aspects of microglial aging at the level of protein interactions and demonstrate a potential role of polyphenols as therapeutics for age-associated dysfunction.

Menopause is an inflection point of age-related immune changes in women

2021 ◽  
pp. 103346
Author(s):  
Aera Han ◽  
Jee Yun Kim ◽  
Joanne Kwak-Kim ◽  
Sung Ki Lee
Keyword(s):  
Inflection Point ◽  
Age Related ◽  
Immune Changes

Toxic effects of cell-free hemoglobin on the microvascular endothelium: implications for pulmonary and non-pulmonary organ dysfunction

2021 ◽  
Author(s):  
Jamie E Meegan ◽  
Julie A. Bastarache ◽  
Lorraine B. Ware
Keyword(s):  
Organ Dysfunction ◽  
Tissue Injury ◽  
Inflammatory Diseases ◽  
Severity Of Illness ◽  
Therapeutic Strategies ◽  
Free Hemoglobin ◽  
Microvascular Endothelium ◽  
Endothelial Inflammation ◽  
Signaling Mechanisms ◽  
Novel Therapeutic Strategies

Levels of circulating cell-free hemoglobin are elevated during hemolytic and inflammatory diseases and contribute to organ dysfunction and severity of illness. Though several studies have investigated the contribution of hemoglobin to tissue injury, the precise signaling mechanisms of hemoglobin-mediated endothelial dysfunction in the lung and other organs are not yet completely understood. The purpose of this review is to highlight the knowledge gained thus far and the need for further investigation regarding hemoglobin-mediated endothelial inflammation and injury in order to develop novel therapeutic strategies targeting the damaging effects of cell-free hemoglobin.

scholarly journals Carbon Monoxide Inhibits Tenascin-C Mediated Inflammation via IL-10 Expression in a Septic Mouse Model

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Md. Jamal Uddin ◽  
Chun-shi Li ◽  
Yeonsoo Joe ◽  
Yingqing Chen ◽  
Qinggao Zhang ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Proinflammatory Cytokines ◽  
Tissue Injury ◽  
Inflammatory Diseases ◽  
Septic Mouse ◽  
Induced Expression ◽  
Tenascin C ◽  
Co Gas

Tenascin-C (TN-C), an extracellular matrix (ECM) glycoprotein, is specifically induced upon tissue injury and infection and during septic conditions. Carbon monoxide (CO) gas is known to exert various anti-inflammatory effects in various inflammatory diseases. However, the mechanisms underlying the effect of CO on TN-C-mediated inflammation are unknown. In the present study, we found that treatment with LPS significantly enhanced TN-C expression in macrophages. CO gas, or treatment with the CO-donor compound, CORM-2, dramatically reduced LPS-induced expression of TN-C and proinflammatory cytokines while significantly increased the expression of IL-10. Treatment with TN-C siRNA significantly suppressed the effects of LPS on proinflammatory cytokines production. TN-C siRNA did not affect the CORM-2-dependent increase of IL-10 expression. In cells transfected with IL-10 siRNA, CORM-2 had no effect on the LPS-induced expression of TN-C and its downstream cytokines. These data suggest that IL-10 mediates the inhibitory effect of CO on TN-C and the downstream production of proinflammatory cytokines. Additionally, administration of CORM-2 dramatically reduced LPS-induced TN-C and proinflammatory cytokines production while expression of IL-10 was significantly increased. In conclusion, CO regulated IL-10 expression and thus inhibited TN-C-mediated inflammationin vitroandin vivo.

Immunodeficiency and Immunomonitoring

2015 ◽  
Vol 38 (1) ◽  
Author(s):  
Harald Renz
Keyword(s):  
Reference Values ◽  
Inflammatory Diseases ◽  
Severe Combined Immunodeficiency ◽  
Cell Receptor ◽  
Chronic Inflammatory Disease ◽  
Age Related ◽  
First Results ◽  
The Usa ◽  
Developing Area ◽  
Excision Circles

AbstractImmunological diagnostics is a rapidly developing area in laboratory medicine. Most recently, major developments in the area of immunodeficiency and the monitoring of chronic inflammatory diseases have been observed. Regarding immuno-monitoring, recently a consensus panel for basic flow cytometry has been published together with age-related reference values. In the USA, the search for severe inherited immunodeficiency diseases (such as severe combined immunodeficiency disease, SCID) is part of neonatal screening procedures. Recently, several US states published first results which are based on the measurement of T-cell receptor excision circles (TRECs). Furthermore, age-dependent reference values for the measurement of IgG subclasses and subclass-specific vaccination antibodies have been published. Monitoring of chronic inflammatory disease focuses on asthma. A novel classification based on the cellular distribution of neutrophils versus eosinophils in induced sputum has been developed. Furthermore, novel biomarkers, such as periostin, are currently under evaluation. Such novel approaches of phenotyping are now the basis of individualized therapeutic approaches in patients with (severe) asthma, who respond to certain biologicals.

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