Modulation of IL-17 and Foxp3 Expression in the Prevention of Autoimmune Arthritis in Mice

©2010 Duarte et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Rheumatoid Arthritis (RA) is a chronic immune mediated disease associated with deregulation of many cell types. It has been reported that different T cell subsets have opposite effects in disease pathogenesis, in particular Th17 and Treg cells. Methodology and Findings: We investigated whether non-depleting anti-CD4 monoclonal antibodies, which have been reported as pro-tolerogenic, can lead to protection from chronic autoimmune arthritis in SKG mice – a recently described animal model of RA – by influencing the Th17/Treg balance. We found that non-depleting anti-CD4 prevented the onset of chronic autoimmune arthritis in SKG mice. Moreover, treated mice were protected from the induction of arthritis up to 60 days following anti-CD4 treatment, while remaining able to mount CD4-dependent immune responses to unrelated antigens. The antibody treatment also prevented disease progression in arthritic mice, although without leading to remission. Protection from arthritis was associated with an increased ratio of Foxp3, and decreased IL-17 producing T cells in the synovia. In vitro assays under Th17-polarizing conditions showed CD4-blockade prevents Th17 polarization, while favoring Foxp3 induction. Conclusions: Non-depleting anti-CD4 can therefore induce long-term protection from chronic autoimmune arthritis in SKG mice through reciprocal changes in the frequency of Treg and Th17 cells in peripheral tissues, thus shifting the balance towards immune tolerance.This work was funded by SUDOE, grant number IMMUNONET-SOE1/1P1/E014, and supported by a research grant from Fundação para a Ciência e Tecnologia (FCT), Portugal (FCT/POCI/SAU-MMO/55974/2004). JD, AA-D, and VGO are funded with scholarships from FCT (SFRH/BD/23631/2005, SFRH/BD/49093/2008, and SFRH/BPD/22575/2005)

Transplantation tolerance: lessons from experimental rodent models

Immunological tolerance or functional unresponsiveness to a transplant is arguably the only approach that is likely to provide long-term graft survival without the problems associated with life-long global immunosuppression. Over the past 50 years, rodent models have become an invaluable tool for elucidating the mechanisms of tolerance to alloantigens. Importantly, rodent models can be adapted to ensure that they reflect more accurately the immune status of human transplant recipients. More recently, the development of genetically modified mice has enabled specific insights into the cellular and molecular mechanisms that play a key role in both the induction and maintenance of tolerance to be obtained and more complex questions to be addressed. This review highlights strategies designed to induce alloantigen specific immunological unresponsiveness leading to transplantation tolerance that have been developed through the use of experimental models

The effect of systematic pediatric care on neonatal mortality and hospitalizations of infants born with oral clefts

<p>Abstract</p> <p>Background</p> <p>Cleft lip and/or palate (CL/P) increase mortality and morbidity risks for affected infants especially in less developed countries. This study aimed at assessing the effects of systematic pediatric care on neonatal mortality and hospitalizations of infants with cleft lip and/or palate (CL/P) in South America.</p> <p>Methods</p> <p>The intervention group included live-born infants with isolated or associated CL/P in 47 hospitals between 2003 and 2005. The control group included live-born infants with CL/P between 2001 and 2002 in the same hospitals. The intervention group received systematic pediatric care between the 7^thand 28^thday of life. The primary outcomes were mortality between the 7^thand 28^thday of life and hospitalization days in this period among survivors adjusted for relevant baseline covariates.</p> <p>Results</p> <p>There were no significant mortality differences between the intervention and control groups. However, surviving infants with associated CL/P in the intervention group had fewer hospitalization days by about six days compared to the associated control group.</p> <p>Conclusions</p> <p>Early systematic pediatric care may significantly reduce neonatal hospitalizations of infants with CL/P and additional birth defects in South America. Given the large healthcare and financial burden of CL/P on affected families and the relatively low cost of systematic pediatric care, improving access to such care may be a cost-effective public policy intervention.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00097149">NCT00097149</a></p

Litter quality and its response to water level drawdown in boreal peatlands at plant species and community level

Changes in the structure of plant communities may have much more impact on ecosystem carbon (C) cycling than any phenotypic responses to environmental changes. We studied these impacts via the response of plant litter quality, at the level of species and community, to persistent water-level (WL) drawdown in peatlands. We studied three sites with different nutrient regimes, and water-level manipulations at two time scales. The parameters used to characterize litter quality included extractable substances, cellulose, holocellulose, composition of hemicellulose (neutral sugars, uronic acids), Klason lignin, CuO oxidation phenolic products, and concentrations of C and several nutrients. The litters formed four chemically distinct groups: non-graminoid foliar litters, graminoids, mosses and woody litters. Direct effects of WL drawdown on litter quality at the species level were overruled by indirect effects via changes in litter type composition. The pristine conditions were characterized by Sphagnum moss and graminoid litters. Short-term (years) responses of the litter inputs to WL drawdown were small. In longterm (decades), total litter inputs increased, due to increased tree litter inputs. Simultaneously, the litter type composition and its chemical quality at the community level greatly changed. The changes that we documented will strongly affect soil properties and C cycle of peatlands.Peer reviewe

Global patterns and drivers of ecosystem functioning in rivers and riparian zones

River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth's biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented "next-generation biomonitoring" by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale.peerReviewe

Mechanism of cellular rejection in transplantation

The explosion of new discoveries in the field of immunology has provided new insights into mechanisms that promote an immune response directed against a transplanted organ. Central to the allograft response are T lymphocytes. This review summarizes the current literature on allorecognition, costimulation, memory T cells, T cell migration, and their role in both acute and chronic graft destruction. An in depth understanding of the cellular mechanisms that result in both acute and chronic allograft rejection will provide new strategies and targeted therapeutics capable of inducing long-lasting, allograft-specific tolerance

Precision measurement of CP\it{CP} violation in the penguin-mediated decay Bs0→ϕϕB_s^{0}\rightarrow\phi\phi

A flavor-tagged time-dependent angular analysis of the decay $B_s^{0}\rightarrow\phi\phi$ is performed using $pp$ collision data collected by the LHCb experiment at % at $\sqrt{s}=13$ TeV, the center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6 fb^{-1}. The $\it{CP}$-violating phase and direct $\it{CP}$-violation parameter are measured to be $\phi_{s\bar{s}s} = -0.042 \pm 0.075 \pm 0.009$ rad and $|\lambda|=1.004\pm 0.030 \pm 0.009$, respectively, assuming the same values for all polarization states of the $\phi\phi$ system. In these results, the first uncertainties are statistical and the second systematic. These parameters are also determined separately for each polarization state, showing no evidence for polarization dependence. The results are combined with previous LHCb measurements using $pp$ collisions at center-of-mass energies of 7 and 8 TeV, yielding $\phi_{s\bar{s}s} = -0.074 \pm 0.069$ rad and $|lambda|=1.009 \pm 0.030$. This is the most precise study of time-dependent $\it{CP}$ violation in a penguin-dominated $B$ meson decay. The results are consistent with $\it{CP}$ symmetry and with the Standard Model predictions.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-001.html (LHCb public pages

Measurement of the Λb0→Λ(1520)μ+μ−\Lambda_{b}^{0}\to \Lambda(1520) \mu^{+}\mu^{-} differential branching fraction

The branching fraction of the rare decay $\Lambda_{b}^{0}\to \Lambda(1520) \mu^{+}\mu^{-}$ is measured for the first time, in the squared dimuon mass intervals, $q^2$, excluding the $J/\psi$ and $\psi(2S)$ regions. The data sample analyzed was collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV, corresponding to a total integrated luminosity of $9\ \mathrm{fb}^{-1}$. The result in the highest$q^{2}$interval,$q^{2} >15.0\ \mathrm{GeV}^2/c^4$, where theoretical predictions have the smallest model dependence, agrees with the predictions.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-050.html (LHCb public pages