Ribavirin modulates the conversion of human <scp>CD</scp>4+ <scp>CD</scp>25−<scp>T</scp> cell to <scp>CD</scp>4+ <scp>CD</scp>25+ <scp>FOXP</scp>3+<scp>T</scp> cell via suppressing interleukin‐10‐producing regulatory <scp>T</scp> cell

Tamaki, Kunihiko; Nakatsuka, Katsuhisa; Shimizu, Mitsuru; Tamura, Hideto; Shinya, Eiji; Atsukawa, Masanori; Harimoto, Hirotomo; Takahashi, Hidemi; Sakamoto, Choitsu

doi:10.1111/imm.12005

Cited by 22 publications

(20 citation statements)

References 67 publications

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“…To differentiate between different scenarios for the origin of non-Gaussianity we should examine further the statistics of the primordial density field. For example, in the absence of curvaton self-interactions the scale-dependence of the non-linearity parameter is given by [13,[37][38][39] n fNL ≡ ∂ ln |f NL | ∂ ln k = 2(n σ − 1) − 2(n ζ − 1) = 2(1 − w χ )(n χ − n φ ) .…”

Section: Discussionmentioning

confidence: 99%

“…The second inflaton slow-roll parameter, η, then affects only the scale-dependence of the power spectrum. Very recently Kobayashi and Takahashi have considered the scale-dependence of both the power spectrum and the non-Gaussianity including mixed inflaton-curvaton models [13]. Note that Langlois and Vernizzi [14] studied linear adiabatic and isocurvature density perturbations allowing for a general inflaton potential, which was then extended [15] to second-and higher-order to study non-Gaussianity in both adiabatic and residual isocurvature density perturbations after inflation and their correlation.…”

Section: Introductionmentioning

confidence: 99%

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Primordial non-Gaussianity from mixed inflaton-curvaton perturbations

Fonseca

Wands

2012

J. Cosmol. Astropart. Phys.

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We characterise the primordial perturbations produced due to both inflaton and curvaton fluctuations in models where the curvaton has a quadratic, cosine or hyperbolic potential, and the inflaton potential is characterised by the usual slow-roll parameters. Isocurvature curvaton field perturbations can produce significant non-Gaussianity in the primordial density field, in contrast with adiabatic inflaton field perturbations which produce negligible non-Gaussianity for canonical scalar fields. A non-self-interacting curvaton with quadratic potential produces a local-type nonGaussianity that is well described by the non-linearity parameter fNL, which may be scale-dependent when the inflaton perturbations dominate the power spectrum. We show how observational bounds on non-linearity parameters and the tensor-scalar ratio can be used to constrain curvaton and inflaton parameters. We find a consistency relation between the bispectrum and trispectrum parameters in a mixed inflaton-curvaton model for a quadratic curvaton potential. Self-interaction terms in the curvaton potential can lead to both a large trispectrum parameter, gNL, and scale-dependence of the non-linearity parameters.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Primordial non-Gaussianity from mixed inflaton-curvaton perturbations

Fonseca

Wands

2012

J. Cosmol. Astropart. Phys.

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“…Previous studies showed the critical roles of IL-10 and TGF-b in the development of Tregs (44,45). Moreover, some evidence showed that IL-10 was an important factor in the resolution of ALI (46,47).…”

Section: Macrophages Induced the Proliferation Of Tregs Through Il-10mentioning

confidence: 98%

Antisense Oligonucleotide Treatment Enhances the Recovery of Acute Lung Injury through IL-10–Secreting M2-like Macrophage-Induced Expansion of CD4+ Regulatory T Cells

Guo

Wen

Qin

et al. 2013

The Journal of Immunology

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MicroRNAs (miRNAs) have been shown as an important regulator in the pathologies of acute lung injury (ALI). However, the potential effect of miRNA-based therapeutic studies in ALI remains poorly understood. We assessed the effect of antisense oligonucleotides (ASOs) against miR-155 on the development of ALI using a murine ALI model. We found that miR-155 ASO treatment could enhance the recovery of ALI as evidenced by accelerated body weight back, reduced level of bronchoalveolar lavage (BAL) protein and proinflammatory cytokines, and reduced number of BAL cells. Adoptive cell transfer assay in RAG1−/− mice showed that CD4+CD25+ regulatory T cells (Tregs) mediated the enhanced recovery of ALI. Mechanistic evidence showed that enhanced expansion of Tregs in vivo, dominantly induced by IL-10–secreting M2-like macrophages, was critical for their elevated proportion in miR-155 ASO-treated ALI mice. Finally, we report that C/EBPβ, a target molecule of miR-155, was upregulated and associated with IL-10 secretion and M2-like phenotype of macrophages. These data provided a previously unknown mechanism for miRNA-based therapy against ALI, which could ultimately aid the understanding of recovery of ALI and the development of new therapeutic strategies against clinical inflammatory lung disease.

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“…ϩ adaptive Treg cells to maintain Th1 cell activity (32). The role of the ribavirin-induced immune response in acting as a selective pressure on hantaviral population and evolution has not yet been addressed.…”

mentioning

confidence: 99%

The Murine Model for Hantaan Virus-Induced Lethal Disease Shows Two Distinct Paths in Viral Evolutionary Trajectory with and without Ribavirin Treatment

Chung

Västermark

Camp

et al. 2013

J Virol

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eIn vitro, ribavirin acts as a lethal mutagen in Hantaan virus (HTNV)-infected Vero E6 cells, resulting in an increased mutation load and viral population extinction. In this study, we asked whether ribavirin treatment in the lethal, suckling mouse model of HTNV infection would act similarly. The HTNV genomic RNA (vRNA) copy number and infectious virus were measured in lungs of untreated and ribavirin-treated mice. In untreated, HTNV-infected mice, the vRNA copy number increased for 10 days postinfection (dpi) and thereafter remained constant through 26 dpi. Surprisingly, in ribavirin-treated, HTNV-infected mice, vRNA levels were similar to those in untreated mice between 10 and 26 dpi. Infectious virus levels, however, were different: in ribavirin-treated mice, the amount of infectious HTNV was significantly decreased relative to that in untreated mice, suggesting that ribavirin reduced the specific infectivity of the virus (amount of infectious virus produced per vRNA copy). Mutational analysis revealed a ribavirin-associated elevation in mutation frequency in HTNV vRNA similar to that previously reported in vitro. Codon-based analyses of rates of nonsynonymous (dN) and synonymous (dS) substitutions in the S segment revealed a positive selection for codons within the HTNV N protein gene in the ribavirin-treated vRNA population. In contrast, the vRNA population in untreated, HTNV-infected mice showed a lower level of diversity, reflecting purifying selection for the wild-type genome. In summary, these experiments show two different evolutionary paths that Hantavirus may take during infection in a lethal murine model of disease, as well as the importance of the in vivo host environment in the evolution of the virus, which was not apparent in our prior in vitro model system.

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Ribavirin modulates the conversion of human CD4⁺ CD25⁻T cell to CD4⁺ CD25⁺ FOXP3⁺T cell via suppressing interleukin‐10‐producing regulatory T cell

Cited by 22 publications

References 67 publications

Primordial non-Gaussianity from mixed inflaton-curvaton perturbations

Primordial non-Gaussianity from mixed inflaton-curvaton perturbations

Antisense Oligonucleotide Treatment Enhances the Recovery of Acute Lung Injury through IL-10–Secreting M2-like Macrophage-Induced Expansion of CD4+ Regulatory T Cells

The Murine Model for Hantaan Virus-Induced Lethal Disease Shows Two Distinct Paths in Viral Evolutionary Trajectory with and without Ribavirin Treatment

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Ribavirin modulates the conversion of human CD4+ CD25−T cell to CD4+ CD25+ FOXP3+T cell via suppressing interleukin‐10‐producing regulatory T cell

Cited by 22 publications

References 67 publications

Primordial non-Gaussianity from mixed inflaton-curvaton perturbations

Primordial non-Gaussianity from mixed inflaton-curvaton perturbations

Antisense Oligonucleotide Treatment Enhances the Recovery of Acute Lung Injury through IL-10–Secreting M2-like Macrophage-Induced Expansion of CD4+ Regulatory T Cells

The Murine Model for Hantaan Virus-Induced Lethal Disease Shows Two Distinct Paths in Viral Evolutionary Trajectory with and without Ribavirin Treatment

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Ribavirin modulates the conversion of human CD4⁺ CD25⁻T cell to CD4⁺ CD25⁺ FOXP3⁺T cell via suppressing interleukin‐10‐producing regulatory T cell