scholarly journals The protective and pathogenic roles of IL-17 in viral infections: friend or foe?

Open Biology ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 190109 ◽  
Author(s):  
Wen-Tao Ma ◽  
Xiao-Ting Yao ◽  
Qun Peng ◽  
De-Kun Chen

Viral infections cause substantial human morbidity and mortality, and are a significant health burden worldwide. Following a viral infection, the host may initiate complex antiviral immune responses to antagonize viral invasion and replication. However, proinflammatory antiviral immune responses pose a great threat to the host if not properly held in check. Interleukin (IL)-17 is a pleiotropic cytokine participating in a variety of physiological and pathophysiological conditions, including tissue integrity maintenance, cancer progression, autoimmune disease development and, more intriguingly, infectious diseases. Abundant evidence suggests that while IL-17 plays a crucial role in enhancing effective antiviral immune responses, it may also promote and exacerbate virus-induced illnesses. Accumulated experimental and clinical evidence has broadened our understanding of the seemingly paradoxical role of IL-17 in viral infections and suggests that IL-17-targeted immunotherapy may be a promising therapeutic option. Herein, we summarize current knowledge regarding the protective and pathogenic roles of IL-17 in viral infections, with emphasis on underlying mechanisms. The various and critical roles of IL-17 in viral infections necessitate the development of therapeutic strategies that are uniquely tailored to both the infectious agent and the infection environment.

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5669
Author(s):  
Akbar Lulu Marzan ◽  
Sarah Elizabeth Stewart

Pancreatic cancer is one of the deadliest cancers worldwide, with a 5-year survival rate of less than 10%. This dismal survival rate can be attributed to several factors including insufficient diagnostics, rapid metastasis and chemoresistance. To identify new treatment options for improved patient outcomes, it is crucial to investigate the underlying mechanisms that contribute to pancreatic cancer progression. Accumulating evidence suggests that extracellular vesicles, including exosomes and microvesicles, are critical players in pancreatic cancer progression and chemoresistance. In addition, extracellular vesicles also have the potential to serve as promising biomarkers, therapeutic targets and drug delivery tools for the treatment of pancreatic cancer. In this review, we aim to summarise the current knowledge on the role of extracellular vesicles in pancreatic cancer progression, metastasis, immunity, metabolic dysfunction and chemoresistance, and discuss their potential roles as biomarkers for early diagnosis and drug delivery vehicles for treatment of pancreatic cancer.


Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 4895
Author(s):  
Ayesha Atiq ◽  
Ishwar Parhar

Clinically, gliomas are classified into four grades, with grade IV glioblastoma multiforme being the most malignant and deadly, which accounts for 50% of all gliomas. Characteristically, glioblastoma involves the aggressive proliferation of cells and invasion of normal brain tissue, outcomes as poor patient prognosis. With the current standard therapy of glioblastoma; surgical resection and radiotherapy followed by adjuvant chemotherapy with temozolomide, it remains fatal, because of the development of drug resistance, tumor recurrence, and metastasis. Therefore, the need for the effective therapeutic option for glioblastoma remains elusive. Previous studies have demonstrated the chemopreventive role of naturally occurring pharmacological agents through preventing or reversing the initiation phase of carcinogenesis or arresting the cancer progression phase. In this review, we discuss the role of natural phytochemicals in the amelioration of glioblastoma, with the aim to improve therapeutic outcomes, and minimize the adverse side effects to improve patient’s prognosis and enhancing their quality of life.


2021 ◽  
Vol 5 (4) ◽  
pp. 195-221
Author(s):  
Katarzyna Nazimek ◽  

<abstract> <p>At present, special efforts are being made to develop the strategies allowing for activation of long-lasting antigen-specific immune tolerance in therapy of allergic and autoimmune diseases. Some of these therapeutic approaches are aimed at modulating cell functions at genetic level by using miRNA-based and miRNA-targeting treatments. Simultaneously, the crucial role of extracellular vesicles as natural miRNA conveyors is highlighted for induction of antigen-specific immune tolerance, especially that they appear to be easily manipulatable for therapeutic applications. Among other immune-related miRNAs, miR-150 is getting special attention as it is differently expressed by immune cells at various stages of their maturation and differentiation. In addition, miR-150 is involved in different signaling cascades orchestrating humoral and cell-mediated mechanisms of both innate and adaptive immune responses. Therefore, miR-150 is considered a master regulator of immunity in mammals. Currently, physiological miR-150-dependent regulatory circuits and causes of their malfunctioning that underlie the pathogenesis of allergic and autoimmune disorders are being unraveled. Thus, present review summarizes the current knowledge of the role of miR-150 in the pathogenesis and complications of these diseases. Furthermore, the involvement of miR-150 in regulation of immune responses to allergens and self-antigens and in induction of antigen-specific immune tolerance is discussed with the special emphasis on the therapeutic potential of this miRNA.</p> </abstract>


2021 ◽  
Vol 14 ◽  
Author(s):  
Saurabh Satija ◽  
Harpreet Kaur ◽  
Murtaza M. Tambuwala ◽  
Prabal Sharma ◽  
Manish Vyas ◽  
...  

Hypoxia is an integral part of tumor microenvironment, caused primarily due to rapidly multiplying tumor cells and a lack of proper blood supply. Among the major hypoxic pathways, HIF-1 transcription factor activation is one of the widely investigated pathways in the hypoxic tumor microenvironment (TME). HIF-1 is known to activate several adaptive reactions in response to oxygen deficiency in tumor cells. HIF-1 has two subunits, HIF-1β (constitutive) and HIF-1α (inducible). The HIF-1α expression is largely regulated via various cytokines (through PI3K-ACT-mTOR signals), which involves the cascading of several growth factors and oncogenic cascades. These events lead to the loss of cellular tumor suppressant activity through changes in the level of oxygen via oxygen-dependent and oxygen-independent pathways. The significant and crucial role of HIF in cancer progression and its underlying mechanisms have gained much attention lately among the translational researchers in the fields of cancer and biological sciences, which have enabled them to correlate these mchanisms with various other disease modalities. In the present review, we have summarized the key findings related to the role of HIF in the progression of tumors.


Author(s):  
Changjun Guo ◽  
Jian He ◽  
Zhi-Min Li ◽  
Yuanyuan Wang ◽  
Chen nan nan ◽  
...  

Exosomes are associated with cancer progression, pregnancy, cardiovascular diseases, central nervous system&ndash;related diseases, immune responses and viral pathogenicity. However, study on the role of exosomes in the immune response of teleost fish, especially antiviral immunity, is limited. Herein, serum-derived exosomes from mandarin fish were used to investigate antiviral effect for the exosomes of teleost fish. Exosomes were isolated from mandarin fish serum by ultracentrifugation could internalize into Mandarin fish fry (MFF-1) cells and inhibited Infectious spleen and kidney necrosis virus (ISKNV) infection. To further investigated the underlying mechanisms of exosomes in inhibiting ISKNV infection. The protein composition of serum-derived exosomes was by analysis mass spectrometry and found that myxovirus resistance 1 (Mx1) was incorporated in the exosomes. Furthermore, the scMx1 protein was proved transferred to the recipient cells though the exosomes. Our results found that the serum-derived exosomes from mandarin fish could inhibit ISKNV replication and suggested an underlying mechanism of the serum-derived exosomes antivirus is that serum-derived exosomes incorporation of the Mx1 protein into exosomes and delivery into recipient cells. This study provided an evidence for the important antiviral role of exosomes in the immune system of teleost fish.


2021 ◽  
Vol 12 ◽  
Author(s):  
Chiel van Geffen ◽  
Astrid Deißler ◽  
Markus Quante ◽  
Harald Renz ◽  
Dominik Hartl ◽  
...  

The immune system is receiving increasing attention for interstitial lung diseases, as knowledge on its role in fibrosis development and response to therapies is expanding. Uncontrolled immune responses and unbalanced injury-inflammation-repair processes drive the initiation and progression of idiopathic pulmonary fibrosis. The regulatory immune system plays important roles in controlling pathogenic immune responses, regulating inflammation and modulating the transition of inflammation to fibrosis. This review aims to summarize and critically discuss the current knowledge on the potential role of regulatory immune cells, including mesenchymal stromal/stem cells, regulatory T cells, regulatory B cells, macrophages, dendritic cells and myeloid-derived suppressor cells in idiopathic pulmonary fibrosis. Furthermore, we review the emerging role of regulatory immune cells in anti-fibrotic therapy and lung transplantation. A comprehensive understanding of immune regulation could pave the way towards new therapeutic or preventive approaches in idiopathic pulmonary fibrosis.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Iwona Wojcik ◽  
David E. Schmidt ◽  
Lisa A. de Neef ◽  
Minke A. E. Rab ◽  
Bob Meek ◽  
...  

AbstractAs a lymphoid organ, the spleen hosts a wide range of immune cell populations, which not only remove blood-borne antigens, but also generate and regulate antigen-specific immune responses. In particular, the splenic microenvironment has been demonstrated to play a prominent role in adaptive immune responses to enveloped viral infections and alloantigens. During both types of immunizations, antigen-specific immunoglobulins G (IgGs) have been characterized by the reduced amount of fucose present on N-linked glycans of the fragment crystallizable (Fc) region. These glycans are essential for mediating the induction of immune effector functions. Therefore, we hypothesized that a spleen may modulate humoral responses and serve as a preferential site for afucosylated IgG responses, which potentially play a role in immune thrombocytopenia (ITP) pathogenesis. To determine the role of the spleen in IgG-Fc glycosylation, we performed IgG subclass-specific liquid chromatography–mass spectrometry (LC–MS) analysis of Fc glycosylation in a large cohort of individuals splenectomized due to trauma, due to ITP, or spherocytosis. IgG-Fc fucosylation was consistently increased after splenectomy, while no effects for IgG-Fc galactosylation and sialylation were observed. An increase in IgG1- and IgG2/3-Fc fucosylation level upon splenectomy has been reported here for the first time, suggesting that immune responses occurring in the spleen may be particularly prone to generate afucosylated IgG responses. Surprisingly, the level of total IgG-Fc fucosylation was decreased in ITP patients compared to healthy controls. Overall, our results suggest a yet unrecognized role of the spleen in either the induction or maintenance of afucosylated IgG responses by B cells.


2020 ◽  
Vol 10 (17) ◽  
pp. 6009
Author(s):  
Malgorzata Anna Krawczyk ◽  
Agata Pospieszynska ◽  
Małgorzata Styczewska ◽  
Ewa Bien ◽  
Sambor Sawicki ◽  
...  

Exosomal heat shock proteins (Hsps) are involved in intercellular communication both in physiological and pathological conditions. They play a role in key processes of carcinogenesis including immune system regulation, cell differentiation, vascular homeostasis and metastasis formation. Thus, exosomal Hsps are emerging biomarkers of malignancies and possible therapeutic targets. Adolescents and young adults (AYAs) are patients aged 15–39 years. This age group, placed between pediatric and adult oncology, pose a particular challenge for cancer management. New biomarkers of cancer growth and progression as well as prognostic factors are desperately needed in AYAs. In this review, we attempted to summarize the current knowledge on the role of exosomal Hsps in selected solid tumors characteristic for the AYA population and/or associated with poor prognosis in this age group. These included malignant melanoma, brain tumors, and breast, colorectal, thyroid, hepatocellular, lung and gynecological tract carcinomas. The studies on exosomal Hsps in these tumors are limited; however; some have provided promising results. Although further research is needed, there is potential for future clinical applications of exosomal Hsps in AYA cancers, both as novel biomarkers of disease presence, progression or relapse, or as therapeutic targets or tools for drug delivery.


2020 ◽  
Vol 21 (24) ◽  
pp. 9690
Author(s):  
Yong-Bin Cho ◽  
In-Gu Lee ◽  
Yong-Hyun Joo ◽  
So-Hee Hong ◽  
Young-Jin Seo

Viral infectious diseases are a significant burden on public health and the global economy, and new viral threats emerge continuously. Since CD4+ and CD8+ T cell responses are essential to eliminating viruses, it is important to understand the underlying mechanisms of anti-viral T cell-mediated immunopathogenesis during viral infections. Remarkable progress in transgenic (Tg) techniques has enabled scientists to more readily understand the mechanisms of viral pathogenesis. T cell receptor (TCR) Tg mice are extremely useful in studying T cell-mediated immune responses because the majority of T cells in these mice express specific TCRs for partner antigens. In this review, we discuss the important studies utilizing TCR Tg mice to unveil underlying mechanisms of T cell-mediated immunopathogenesis during viral infections.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Zhaoji Pan ◽  
Yiqing Tian ◽  
Guoping Niu ◽  
Chengsong Cao

Mesenchymal stem cells (MSCs) have been declared to not only participate in wound repair but also affect tumor progression. Tumor-associated MSCs, directly existing in the tumor microenvironment, play a critical role in tumor initiation, progression, and development. And different tumor-derived MSCs have their own unique characteristics. In this review, we mainly describe and discuss recent advances in our understanding of the emerging role of gastric cancer-derived MSC-like cells (GC-MSCs) in regulating gastric cancer progression and development, as well as the bidirectional influence between GC-MSCs and immune cells of the tumor microenvironment. Moreover, we also discuss the potential biomarker and therapeutic role of GC-MSCs. It is anticipated that new and deep insights into the functionality of GC-MSCs and the underlying mechanisms will promote the novel and promising therapeutic strategies against gastric cancer.


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