Immunoregulatory molecules are master regulators of inflammation during the immune response

Fuente, Hortensia de la; Cibrián, Danay; Sánchez-Madrid, Francisco

doi:10.1016/j.febslet.2012.07.032

Cited by 34 publications

(35 citation statements)

References 133 publications

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“…However our findings do not indicate causality between expression of CTLA-4/PD-1 and poor outcome: on one hand it is possible that high viremia triggers overwhelming inflammation thereby causing CTLA-4 and PD-1 upregulation on T cells, and on the other hand, it is plausible to assume that expression of these molecules inhibits T cell function leading to poor viral clearance. Indeed, both possibilities have been reported in the literature 13,28 and their elucidation requires evaluation of CTLA-4 function during EVD in adequate infection models. Interestingly, during severe EVD both PD-1 and CTLA-4 are upregulated while in other acute human infections such as hantavirus disease and pediatric influenza only CTLA-4 but not PD-1 was upregulated 13,14 .…”

Section: Main Textmentioning

confidence: 99%

Unique human immune signature of Ebola virus disease in Guinea

Ruibal

Oestereich

Lüdtke

et al. 2016

Nature

166

195

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Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD1. In particular, very little is known about human immune responses to Ebola virus (EBOV)2,3. Here, we have for the first time evaluated the physiology of the human T cell immune response in EVD patients at the time of admission at the Ebola Treatment Center (ETC) in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we have identified an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by high percentage of CD4 and CD8 T cells expressing the inhibitory molecules cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1), which was correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation despite comparable overall T cell activation. Concommittant with virus clearance, survivors mounted a robust EBOV-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.

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Section: Main Textmentioning

confidence: 99%

Unique human immune signature of Ebola virus disease in Guinea

Ruibal

Oestereich

Lüdtke

et al. 2016

Nature

166

195

View full text Add to dashboard Cite

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“…Although it was less statistically significant, insulin receptor signaling was extracted as the hypertrophy-related pathway, suggesting that the alteration of the signaling, such as insulin resistance, which is often associated with common diseases and/or age-related disorders, may contribute to hypertrophy 35) . Pentose phosphate and GADD45 signaling pathways have been described to be involved in oxidative stress response and inflammation 36,37) . These pathways have not been described in the context of LF hypertrophy but are attractive points of views from which to study LF hypertrophy.…”

Section: A B Cmentioning

confidence: 99%

MicroRNA transcriptome analysis on hypertrophy of ligamentum flavum in patients with lumbar spinal stenosis

Mori

Sakai²,

Kayano

et al. 2017

Spine Surg Relat Res

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Abstract:Introduction: Molecular pathways involved in ligamentum flavum (LF) hypertrophy are still unclarified. The purpose of this study was to characterize LF hypertrophy by microRNA (miRNA) profiling according to the classification of lumbar spinal stenosis (LSS).Methods: Classification of patients with LSS into ligamentous and non-ligamentous cases was conducted by clinical observation and the morphometric parameter adopting the LF/spinal canal area ratio (LSAR) from measurements of magnetic resonance imaging (MRI) T2 weighed images. LF from patients with ligamentous stenosis (n=10) were considered as the degenerative hypertrophied samples, and those from patients with non-ligamentous LSS (n=7) and lumbar disc herniation (LDH, n=3) were used as non-hypertrophied controls. Profiling of miRNA from all samples was conducted by Agilent microarray. Microarray data analysis was performed with GeneSpring GX, and pathway analysis was performed using Ingenuity Pathway Analysis.Results: The mean LSAR in the ligamentous group was significantly higher than that in the control group (0.662±0.154 vs 0.301±0.068, p=0.0000171). Ten significantly differentially expressed miRNA were identified and taken as a signature of LF hypertrophy: nine miRNA showed down-regulated expression, and one showed up-regulated expression in the ligamentous LF. Among those, miR-423-5p (rs=-0.473, p<0.05), miR-4306 (rs=-0.628, p<0.01), miR-516b-5p (rs=-0.629, p<0.01), and miR-497-5p (rs=0.461, p<0.05) were correlated to the LSAR. Pathway analysis predicted aryl hydrocarbon receptor signaling (p<0.01), Wnt/β-catenin signaling (p<0.01), and insulin receptor signaling (p<0.05) as canonical pathways associated with the miRNA signature.Conclusions: Classification based on quantification of the MRI axial image is useful for studying hypertrophy of the LF. Aryl hydrocarbon receptor and Wnt/β-catenin signaling may be involved in LF hypertrophy.

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“…Finally, Galectins (Gal) are a family of carbohydrate-binding proteins with an affinity for β-galactosides, and Gal-1 and -3 exhibit profound and unique modulatory activities on immune effector functions by controlling cell activation, cytokine synthesis and viability through cross-linking of the cognate receptors on the surface of lymphatic cells (de la Fuente et al, 2012). The interaction of MSC-membrane-bound or secreted Gal-1 and Gal-3 with their receptors on T cells induces tolerogenic signals, resulting in T-cell suppression (Sioud, 2011).…”

Section: Paracrine Signalingmentioning

confidence: 99%

How stem cells speak with host immune cells in inflammatory brain diseases

Pluchino

Cossetti

2013

Glia

111

109

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Advances in stem cell biology have raised great expectations that diseases and injuries of the central nervous system (CNS) may be ameliorated by the development of non-hematopoietic stem cell medicines. Yet, the application of adult stem cells as CNS therapeutics is challenging and the interpretation of some of the outcomes ambiguous. In fact, the initial idea that stem cell transplants work only via structural cell replacement has been challenged by the observation of consistent cellular signaling between the graft and the host. Cellular signaling is the foundation of coordinated actions and flexible responses, and arises via networks of exchanging and interacting molecules that transmit patterns of information between cells. Sustained stem cell graft-to-host communication leads to remarkable trophic effects on endogenous brain cells and beneficial modulatory actions on innate and adaptive immune responses in vivo, ultimately promoting the healing of the injured CNS. Among a number of adult stem cell types, mesenchymal stem cells (MSCs) and neural stem/precursor cells (NPCs) are being extensively investigated for their ability to signal to the immune system upon transplantation in experimental CNS diseases. Here, we focus on the main cellular signaling pathways that grafted MSCs and NPCs use to establish a therapeutically relevant cross talk with host immune cells, while examining the role of inflammation in regulating some of the bidirectionality of these communications. We propose that the identification of the players involved in stem cell signaling might contribute to the development of innovative, high clinical impact therapeutics for inflammatory CNS diseases.

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Immunoregulatory molecules are master regulators of inflammation during the immune response

Cited by 34 publications

References 133 publications

Unique human immune signature of Ebola virus disease in Guinea

Unique human immune signature of Ebola virus disease in Guinea

MicroRNA transcriptome analysis on hypertrophy of ligamentum flavum in patients with lumbar spinal stenosis

How stem cells speak with host immune cells in inflammatory brain diseases

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