Interleukin-15 in Outcomes of Pregnancy

Interleukin-15 (IL-15) is a pleiotropic cytokine that classically acts to support the development, maintenance, and function of killer lymphocytes. IL-15 is abundant in the uterus prior to and during pregnancy, but it is subject to tight spatial and temporal regulation. Both mouse models and human studies suggest that homeostasis of IL-15 is essential for healthy pregnancy. Dysregulation of IL-15 is associated with adverse outcomes of pregnancy. Herein, we review producers of IL-15 and responders to IL-15, including non-traditional responders in the maternal uterus and fetal placenta. We also review regulation of IL-15 at the maternal–fetal interface and propose mechanisms of action of IL-15 to facilitate additional study of this critical cytokine in the context of pregnancy.

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453 Novel combination immunotherapy for boosting and priming immune responses in pancreatic cancer: strong anti-tumour effects with interleukin-15 and CD40 agonist treatment

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0453 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A480-A480

Author(s):

Jonas Van Audenaerde ◽

Elly Marcq ◽

Bianca von Scheidt ◽

Ashleigh Davey ◽

Amanda Oliver ◽

...

Keyword(s):

Pancreatic Cancer ◽

T Cells ◽

Dendritic Cells ◽

Natural Killer ◽

Mouse Models ◽

Cd8 T Cells ◽

Tumour Growth ◽

Immune Memory ◽

Combination Immunotherapy ◽

Interleukin 15

BackgroundWith the poorest 5-year survival of all cancers, improving treatment for pancreatic cancer is one of the biggest challenges in cancer research. In this era of combination immunotherapies, we sought to explore the potential of combining both priming and activation of the immune system. To achieve this, we combined a CD40 agonist with interleukin-15 and tested its potential in pancreatic cancer.MethodsTwo different mouse models of pancreatic cancer were used to assess the potential of this combination regimen. Therefore, effects on tumour growth kinetics and survival were charted. Differential effects on immune signatures was investigated using RNA sequencing. Functional immune subset involvement was tested using different immune depletion experiments and multicolour flow cytometry in different relevant immune sites. Immune memory was checked using re-challenge experiments.ResultsWe demonstrated profound reduction in tumour growth and increased survival of mice with the majority of mice being cured when both agents were combined, including an unprecedented dose reduction of CD40 agonist without losing any efficacy (fig 1). RNA sequencing analysis showed involvement of natural killer cell and T cell mediated anti-tumour responses and the importance of antigen-presenting cell pathways. This combination resulted in enhanced infiltration of tumours by both cytotoxic T cells and natural killer cells, as well as a striking increase in the ratio of CD8+ T cells over T regulatory cells. We also observed a significant increase in numbers of dendritic cells in tumour draining lymph nodes, particularly CD103+ dendritic cells with cross-presentation potential. A critical role for CD8+ T cells and involvement of natural killer cells in the anti-tumour effect was highlighted. Importantly, strong immune memory was established, with an increase in memory CD8+ T cells only when both interleukin-15 and the CD40 agonist were combined.Abstract 453 Figure 1Tumour kinetics and survival in Panc02 (left) and KPC (right) pancreatic cancer mouse modelsConclusionsWe demonstrated profound synergistic anti-tumour effects upon combination of CD40 agonist and interleukin-15 treatment in mouse models of pancreatic cancer. This preclinical data supports initiation of a first-in-human clinical trial with this combination immunotherapy strategy in pancreatic cancer.

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15-Lipoxygenase-2 Deficiency Induces a Dysfunction in Macrophages That Can Be Restored by Salidroside

10.21203/rs.3.rs-144514/v1 ◽

2021 ◽

Author(s):

Rong Huang Huang ◽

Tingting Li Li ◽

Xi Yong Yong ◽

Huling Wen Wen ◽

Xing Zhou Zhou ◽

...

Keyword(s):

Natural Product ◽

Signaling Pathway ◽

Therapeutic Strategy ◽

Caspase 3 ◽

Mechanisms Of Action ◽

Rna Seq ◽

Immunological Function ◽

Tnf Α ◽

And Function ◽

Genetic Strategies

Abstract 15-Lipoxygenase-2(15-LOX-2) is thought to regulate inflammation and immunological function however, its mechanisms of action are still unclear. Furthermore, it has been reported that salidroside has anti inflammatory properties , but its role in macrophage function has not been understood yet In this study, we aimed to determine how 15-LOX-2 expression level s affect the function of macrophages and the effect of salidroside on 15-LOX-2 deficient macrophages We used multiple functional genetic strategies to determine 15-LOX-2 function in macrophages. 15-LOX-2 deficiency promotes phagocytosis and proliferation of macrophages and impairs their apoptosis Mechanistically, t he expression levels of cyclophilinB (CypB) were upregulated in 15-LOX-2 deficient Ana 1 macrophages, whereas those of caspase 3 were down regulated. Furthermore, RNA-seq analysis showed that inflammation, complement, and TNF-α signaling pathway s were all activated in 15-LOX-2 deficient Ana 1 macrophages. Treatment of 15-LOX-2 deficient macrophages with salidroside, a natural product derived from Rhodiola species, effectively reversed the effects of 15-LOX-2 deficiency on caspase 3 and CypB levels, as well as on apoptosis and proliferation. In conclusion, our study shows that there is a newly identified link between 15-LOX-2 deficiency and salidroside in regulating macrophage survival, proliferation, and function. Salidroside may be a promising therapeutic strategy for treating inflammation related diseases resulting from 15-LOX-2 deficiency.

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Severity of Demyelinating and Axonal Neuropathy Mouse Models Is Modified by Genes Affecting Structure and Function of Peripheral Nodes

Cell Reports ◽

10.1016/j.celrep.2017.03.009 ◽

2017 ◽

Vol 18 (13) ◽

pp. 3178-3191 ◽

Cited By ~ 11

Author(s):

Kathryn H. Morelli ◽

Kevin L. Seburn ◽

David G. Schroeder ◽

Emily L. Spaulding ◽

Loiuse A. Dionne ◽

...

Keyword(s):

Mouse Models ◽

Axonal Neuropathy ◽

Structure And Function ◽

And Function

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When the past informs our future

eLife ◽

10.7554/elife.67169 ◽

2021 ◽

Vol 10 ◽

Author(s):

Abigail LaBella

Keyword(s):

Immune System ◽

The Past ◽

Healthy Pregnancy ◽

Maternal Fetal Interface

Comparing the genes expressed at the maternal-fetal interface in different species helps to pinpoint those that contribute to a healthy pregnancy by regulating the activity of the immune system.

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Cannabidiol for the Treatment of Epilepsy: An Overview of Possible Mechanisms of Action and Preclinical and Human Studies

Handbook of Cannabis and Related Pathologies ◽

10.1016/b978-0-12-800756-3.00094-6 ◽

2017 ◽

pp. 795-801

Author(s):

R. Guimarães dos Santos ◽

J.E.C. Hallak ◽

A.W. Zuardi ◽

A.C. de Souza Crippa ◽

J.A. de Souza Crippa

Keyword(s):

Mechanisms Of Action ◽

Human Studies ◽

Treatment Of Epilepsy

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Quantitative Analysis of Retinal Structure and Function in Two Chromosomally Altered Mouse Models of Down Syndrome

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.61.5.25 ◽

2020 ◽

Vol 61 (5) ◽

pp. 25

Author(s):

Daniella B. Victorino ◽

Jonah J. Scott-McKean ◽

Mark W. Johnson ◽

Alberto C. S. Costa

Keyword(s):

Down Syndrome ◽

Quantitative Analysis ◽

Mouse Models ◽

Structure And Function ◽

Retinal Structure ◽

And Function

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Genetic mouse models to study blood–brain barrier development and function

Fluids and Barriers of the CNS ◽

10.1186/2045-8118-10-3 ◽

2013 ◽

Vol 10 (1) ◽

pp. 3 ◽

Cited By ~ 15

Author(s):

Fabien Sohet ◽

Richard Daneman

Keyword(s):

Blood Brain Barrier ◽

Mouse Models ◽

Brain Barrier ◽

Blood Brain ◽

And Function ◽

Genetic Mouse Models

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Androgen receptor knockout and knock-in mouse models

Journal of Molecular Endocrinology ◽

10.1677/jme-08-0122 ◽

2008 ◽

Vol 42 (1) ◽

pp. 11-17 ◽

Cited By ~ 43

Author(s):

S Kerkhofs ◽

S Denayer ◽

A Haelens ◽

F Claessens

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Steroid Hormones ◽

Mouse Models ◽

Reproductive Development ◽

Androgen Insensitivity Syndrome ◽

Androgen Insensitivity ◽

And Function ◽

Insight Into ◽

Working Mechanisms

Androgens play an important role in male reproductive development and function. These steroid hormones mediate their actions by binding to the androgen receptor (AR). Diseases such as androgen insensitivity syndrome, prostate cancer, Kennedy's disease, and infertility can be caused by mutations in the AR. To get a better insight into the molecular working mechanisms of the AR, several knockout and knock-in mouse models have been developed. These models are reviewed here and are compared with human diseases.

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