scholarly journals Mechanobiological Principles Influence the Immune Response in Regeneration: Implications for Bone Healing

2021 ◽  
Vol 9 ◽  
Author(s):  
Raphael S. Knecht ◽  
Christian H. Bucher ◽  
Sophie Van Linthout ◽  
Carsten Tschöpe ◽  
Katharina Schmidt-Bleek ◽  
...  
Keyword(s):  
Immune Response ◽  
Extracellular Matrix ◽  
Immune Responses ◽  
Tissue Regeneration ◽  
Immune Cells ◽  
Material Properties ◽  
Treatment Options ◽  
Hematopoietic Cells ◽  
Therapeutic Approaches ◽  
New Treatment

A misdirected or imbalanced local immune composition is often one of the reasons for unsuccessful regeneration resulting in scarring or fibrosis. Successful healing requires a balanced initiation and a timely down-regulation of the inflammation for the re-establishment of a biologically and mechanically homeostasis. While biomaterial-based approaches to control local immune responses are emerging as potential new treatment options, the extent to which biophysical material properties themselves play a role in modulating a local immune niche response has so far been considered only occasionally. The communication loop between extracellular matrix, non-hematopoietic cells, and immune cells seems to be specifically sensitive to mechanical cues and appears to play a role in the initiation and promotion of a local inflammatory setting. In this review, we focus on the crosstalk between ECM and its mechanical triggers and how they impact immune cells and non-hematopoietic cells and their crosstalk during tissue regeneration. We realized that especially mechanosensitive receptors such as TRPV4 and PIEZO1 and the mechanosensitive transcription factor YAP/TAZ are essential to regeneration in various organ settings. This indicates novel opportunities for therapeutic approaches to improve tissue regeneration, based on the immune-mechanical principles found in bone but also lung, heart, and skin.

scholarly journals The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Tian-Yu Lei ◽  
Ying-Ze Ye ◽  
Xi-Qun Zhu ◽  
Daniel Smerin ◽  
Li-Juan Gu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Ischaemic Stroke ◽  
Immune Cells ◽  
Tissue Injury ◽  
Recovery Period ◽  
Vital Functions ◽  
Anti Inflammatory

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

New Therapeutics for Ulcerative Colitis

2021 ◽  
Vol 72 (1) ◽  
pp. 199-213
Author(s):  
Robert P. Hirten ◽  
Bruce E. Sands
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Disease ◽  
Clinical Remission ◽  
Treatment Options ◽  
Treatment Modalities ◽  
Therapeutic Approaches ◽  
Stages Of Development ◽  
The Future ◽  
New Treatment ◽  
Novel Therapeutic

Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease of the colon with a variable course. Despite advances in treatment, only approximately 40% of patients achieve clinical remission at the end of a year, prompting the exploration of new treatment modalities. This review explores novel therapeutic approaches to UC, including promising drugs in various stages of development, efforts to maximize the efficacy of currently available treatment options, and non-medication-based modalities. Treatment approaches which show promise in impacting the future of UC management are highlighted.

scholarly journals Unlocking the Potential of Vaccines Built on Messenger RNA

2021 ◽  
pp. 160-197
Author(s):  
Elena Locci ◽  
Silvia Raymond
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Side Effects ◽  
Immune Responses ◽  
Messenger Rna ◽  
Healthy Tissue ◽  
Therapeutic Approaches ◽  
Inflammatory Reactions ◽  
Discontinuation Of Treatment ◽  
Keywords Cancer

In recent years, immunotherapy has revolutionized the treatment of cancer; however, inflammatory reactions in healthy tissues often have side effects that can be serious and lead to permanent discontinuation of treatment. This toxicity is not yet well understood and is a major obstacle to the use of immunotherapy. When the immune system is so severely activated, the resulting inflammatory reaction can have detrimental effects and sometimes serious damage to healthy tissue. We wanted to know if there was a difference between an optimal immune response that aims to kill cancer and an unwanted response that could affect healthy tissue. Identifying the distinctive elements between these two immune responses allows the development of new, more effective and less toxic therapeutic approaches. Keywords: Cancer; Cells; Tissues, Tumors; Prevention, Prognosis; Diagnosis; Imaging; Screening; Treatment; Management

scholarly journals Dual-Wavelength Photosensitive Nano-in-Micro Scaffold Regulates Innate and Adaptive Immune Responses for Osteogenesis

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Qin Zhao ◽  
Miusi Shi ◽  
Chengcheng Yin ◽  
Zifan Zhao ◽  
Jinglun Zhang ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
T Cell Response ◽  
Dual Wavelength ◽  
M2 Macrophage ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

AbstractThe immune response of a biomaterial determines its osteoinductive effect. Although the mechanisms by which some immune cells promote regeneration have been revealed, the biomaterial-induced immune response is a dynamic process involving multiple cells. Currently, it is challenging to accurately regulate the innate and adaptive immune responses to promote osteoinduction in biomaterials. Herein, we investigated the roles of macrophages and dendritic cells (DCs) during the osteoinduction of biphasic calcium phosphate (BCP) scaffolds. We found that osteoinductive BCP directed M2 macrophage polarization and inhibited DC maturation, resulting in low T cell response and efficient osteogenesis. Accordingly, a dual-targeting nano-in-micro scaffold (BCP loaded with gold nanocage, BCP-GNC) was designed to regulate the immune responses of macrophages and DCs. Through a dual-wavelength photosensitive switch, BCP-GNC releases interleukin-4 in the early stage of osteoinduction to target M2 macrophages and then releases dexamethasone in the later stage to target immature DCs, creating a desirable inflammatory environment for osteogenesis. This study demonstrates that biomaterials developed to have specific regulatory capacities for immune cells can be used to control the early inflammatory responses of implanted materials and induce osteogenesis.

scholarly journals Type I and II Interferons in the Anti-Tumor Immune Response

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1037
Author(s):  
Sarah E. Fenton ◽  
Diana Saleiro ◽  
Leonidas C. Platanias
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Tumor Response ◽  
Cancer Surveillance ◽  
Type I ◽  
Type Ii ◽  
Malignant Cells ◽  
Therapeutic Approaches ◽  
Feedback Mechanisms ◽  
Essential Components

The interferons (IFNs) are essential components of the immune response against infections and malignancies. IFNs are potent promoters of the anti-tumor response, but there is also evidence that feedback mechanisms regulated by IFNs negatively control immune responses to avoid hyper-activation and limit inflammation. This balance of responses plays an important role in cancer surveillance, immunoediting and response to anticancer therapeutic approaches. Here we review the roles of both type I and type II IFNs on the control of the immune response against malignancies in the context of effects on both malignant cells and cells of the immune system in the tumor microenvironment.

scholarly journals Macrophages and Extracellular Matrix in Breast Cancer: Partners in Crime or Protective Allies?

2021 ◽  
Vol 11 ◽  
Author(s):  
Claire Deligne ◽  
Kim S. Midwood
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Extracellular Matrix ◽  
Tumor Growth ◽  
Immune Cells ◽  
Current Knowledge ◽  
Immune Surveillance ◽  
Tumor Stroma ◽  
The Matrix ◽  
And Function

Solid cancers such as breast tumors comprise a collection of tumor, stromal and immune cells, embedded within a network of tumor-specific extracellular matrix. This matrix is associated with tumor aggression, treatment failure, chemo- and radio-resistance, poor survival and metastasis. Recent data report an immunomodulatory role for the matrix in cancer, via the creation of niches that control the migration, localization, phenotype and function of tumor-infiltrating immune cells, ultimately contributing to escape of immune surveillance. Macrophages are crucial components of the immune infiltrate in tumors; they are associated with a poor prognosis in breast cancer and contribute to shaping the anti-tumor immune response. We and others have described how matrix molecules commonly upregulated within the tumor stroma, such as tenascin-C, fibronectin and collagen, exert a complex influence over macrophage behavior, for example restricting or enhancing their infiltration into the tumor, and driving their polarization towards or away from a pro-tumoral phenotype, and how in turn macrophages can modify matrix production in the tumor to favor tumor growth and metastasis. Targeting specific domains of matrix molecules to reinstate an efficient anti-tumor immune response, and effectively control tumor growth and spread, is emerging as a promising field offering a new angle for cancer therapy. Here, we review current knowledge on the interactions between tumor-associated macrophages and matrix molecules that occur within the tumor microenvironment of breast cancer, and discuss how these pathways can be targeted for new immunotherapies for hard to treat, desmoplastic tumors.

scholarly journals A Systematic Literature Review of Current Therapeutic Approaches for COVID-19 Patients

2020 ◽  
pp. 13-25 ◽  
Author(s):  
Saber Soltani ◽  
Amir Mohammad Zakeri ◽  
Mohammad Reza Karimi ◽  
Sara Akhavan Rezayat ◽  
Fateme Zomorodi Anbaji ◽  
...  
Keyword(s):  
Literature Review ◽  
Supportive Care ◽  
Web Of Science ◽  
Drug Research ◽  
Treatment Options ◽  
Antiviral Agents ◽  
Therapeutic Approaches ◽  
Improved Outcomes ◽  
New Treatment ◽  
Novel Coronavirus

Background: In December 2019, the pneumonia outbreak reported in Wuhan, Hubei Province, China. WHO introduced a novel coronavirus and the virus named Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) in January 2020. There are not any specific antiviral agents for coronavirus disease 19 (COVID‐19). Objective: Our review aimed to discuss treatment options and the efficacy of currently prescribed drugs and supportive care in COVID‐19 patients. Study Design: A literature review of the articles in the Web of Science, PubMed, Scopus and EMBASE conducted. Results: Lopinavir/ritonavir combination was the most frequently used drug, followed by Arbidol and Oseltamivir and Methylprednisolone. Lopinavir/Ritonavir outcome showed the fever and respiratory infection improve in day two and day eight, respectively. Also, negative PCR of SARS‐CoV‐2 in days six and 7day was seen and finally these patients discharged in 10 days. Conclusions: Lopinavir/Ritonavir was the most improving administrated antiviral combination, which might be a good option for COVID-19 due to its availability. Although supportive care such as O2 supplementary and IV fluid therapy has improved outcomes. There are not evidence for suggesting a new treatment or a new drug, which mean the necessity of further investigations for drug research in a clinical trial for a conclusion about the optimum treatment.

scholarly journals Tissue-autonomous immune response regulates stress signalling during hypertrophy

2019 ◽  
Author(s):  
Robert Krautz ◽  
Dilan Khalili ◽  
Ulrich Theopold
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Stress Response ◽  
Immune Responses ◽  
Salivary Glands ◽  
Mapk Pathway ◽  
Therapeutic Approaches ◽  
Direct Inhibition ◽  
Systemic Immune Response ◽  
Stress Accumulation

AbstractPostmitotic tissues are incapable of replacing damaged cells through proliferation, but need to rely on buffering mechanisms to prevent tissue disintegration. By constitutively activating the Ras/MAPK-pathway via RasV12-overexpression in the postmitotic salivary glands of Drosophila larvae, we overrode the glands adaptability to growth signals, induced hypertrophy and stress accumulation. This allowed us to decipher a novel, spatio-temporally regulated interaction between the JNK-stress response and a genuine tissue-autonomous immune response. Central to this interaction is the direct inhibition of JNK-signalling by the antimicrobial peptide Drosomycin, which blocks programmed cell death and prevents recognition of the stressed tissue by the systemic immune response. While this mechanism might allow growing salivary glands to cope with temporary stress, continuous expression of Drosomycin favors survival of unrestricted, hypertrophic RasV12-glands. Our findings indicate the necessity for refined therapeutic approaches that fundamentally acknowledge detrimental effects that stimulated immune responses have on tissues coping with damage and stress.

scholarly journals Tissue-autonomous immune response regulates stress signalling during hypertrophy

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Robert Krautz ◽  
Dilan Khalili ◽  
Ulrich Theopold
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Salivary Glands ◽  
Feedback Loop ◽  
Mapk Pathway ◽  
Therapeutic Approaches ◽  
Jnk Pathway ◽  
Immune Effector ◽  
Tissue Integrity ◽  
Stress Signalling

Postmitotic tissues are incapable of replacing damaged cells through proliferation, but need to rely on buffering mechanisms to prevent tissue disintegration. By constitutively activating the Ras/MAPK-pathway via RasV12-overexpression in the postmitotic salivary glands of Drosophila larvae, we overrode the glands adaptability to growth signals and induced hypertrophy. The accompanied loss of tissue integrity, recognition by cellular immunity and cell death are all buffered by blocking stress signalling through a genuine tissue-autonomous immune response. This novel, spatio-temporally tightly regulated mechanism relies on the inhibition of a feedback-loop in the JNK-pathway by the immune effector and antimicrobial peptide Drosomycin. While this interaction might allow growing salivary glands to cope with temporary stress, continuous Drosomycin expression in RasV12-glands favors unrestricted hypertrophy. These findings indicate the necessity to refine therapeutic approaches that stimulate immune responses by acknowledging their possible, detrimental effects in damaged or stressed tissues.

scholarly journals A comprehensive logic-based model of the human immune system to study the dynamics responses to mono- and coinfections

2020 ◽  
Author(s):  
Bhanwar Lal Puniya ◽  
Robert Moore ◽  
Akram Mohammed ◽  
Rada Amin ◽  
Alyssa La Fleur ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Responses ◽  
Immune Cells ◽  
Computational Models ◽  
Single Infection ◽  
Human Immune System ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Human Immune

AbstractThe human immune system, which protects against pathogens and diseases, is a complex network of cells and molecules. The effects of complex dynamical interactions of pathogens and immune cells on the immune response can be studied using computational models. However, a model of the entire immune system is still lacking. Here, we developed a comprehensive computational model that integrates innate and adaptive immune cells, cytokines, immunoglobulins, and nine common pathogens from different classes of virus, bacteria, parasites, and fungi. This model was used to investigate the dynamics of the immune system under two scenarios: (1) single infection with pathogens, and (2) various medically relevant pathogen coinfections. In coinfections, we found that the order of infecting pathogens has a significant impact on the dynamics of cytokines and immunoglobulins. Thus, our model provides a tool to simulate immune responses under different dosage of pathogens and their combinations, which can be further extended and used as a tool for drug discovery and immunotherapy. Furthermore, the model provides a comprehensive and simulatable blueprint of the human immune system as a result of the synthesis of the vast knowledge about the network-like interactions of various components of the system.

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