Foxp3
regulatory T cells (Treg) maintain the integrity of the organism by preventing excessive immune responses. These cells protect against autoimmune diseases but are also important regulators of ...other immune responses including inflammation, allergy, infection, and tumors. Furthermore, they exert non-immune functions such as tissue repair and regeneration. In the periphery, Foxp3
Treg have emerged as a highly heterogeneous cell population with distinct molecular and functional properties. Foxp3
Treg mainly develop within the thymus where they receive instructive signals for their differentiation. Recent studies have revealed that thymic Treg are also heterogeneous with two distinct precursors that give rise to mature Foxp3
Treg exhibiting non-overlapping regulatory activities characterized by a differential ability to control different types of autoimmune reactions. Furthermore, the thymic Treg cell pool is not only composed of newly developing Treg, but also contain a large fraction of recirculating peripheral cells. Here, we review the two pathways of thymic Treg cell differentiation and their potential impact on Treg activity in the periphery. We also summarize our current knowledge on recirculating peripheral Treg in the thymus.
PM10 and PM2.5 levels, concentrations of major components, trace elements, pH, conductivity and source apportionment were evaluated from samples collected during 2009 at three different locations ...(rural, urban and urban-traffic) in Navarra (North of Spain). Mean particulate matter concentrations were below the annual limit value for PM10 and annual target value for PM2.5 established by the European Directive 2008/50/EC and similar to those recorded at other locations in the North of Spain. The major components of PM10 in the three sampling stations were, by order of importance, OC
+
EC, NO3- and non-marine sulphate (nmSO42-), whereas the major components of PM2.5 were OC
+
EC, nmSO42- and NO3-. ΔpH values indicated that PM2.5 samples were more acidic than PM10 ones. The 90–96% of total trace elements contribution in PM2.5 and PM10 were described by P, Ti, Cr, Mn, Ni, Cu, Zn, Sr, Sn, Ba and Pb. Concentrations of those elements were lower than values obtained in Pamplona in 2002–2004 and similar to those found in other sub-urban and urban Spanish cities. PMF model identified 5 principle sources for PM10 and PM2.5 in Iturrama and Plaza de la Cruz (crustal, secondary sulphate, secondary nitrate, traffic and sea-salt aerosols) and 4 sources for PM10 in Bertiz (crustal, secondary sulphate, secondary nitrate and sea-salt).
► PM
10 and PM
2.5 characterisation in rural, urban and traffic sites in North of Spain. ► Decrease in PM
10 levels was found from 2005 to 2009 in Pamplona. ► European air mass transport related to the 80% of exceedances in 2009. ► Increasing levels of OM
+
EC, mineral dust, Cu, Mn, Sb and Sn were found from rural to traffic site. ► PMF identified 5 sources in Pamplona and 4 in rural site.
Thymically-derived Foxp3
+
regulatory T cells (T
reg
) critically control immunological tolerance. These cells are generated in the medulla through high affinity interactions with medullary thymic ...epithelial cells (mTEC) expressing the Autoimmune regulator (Aire). Recent advances have revealed that thymic T
reg
contain not only developing but also recirculating cells from the periphery. Although Aire is implicated in the generation of Foxp3
+
T
reg
, its role in the biology of recirculating T
reg
remains elusive. Here, we show that Aire regulates the suppressive signature of recirculating T
reg
independently of the remodeling of the medullary 3D organization throughout life where T
reg
reside. Accordingly, the adoptive transfer of peripheral Foxp3
+
T
reg
in
Aire
KO
recipients led to an impaired suppressive signature upon their entry into the thymus. Furthermore, recirculating T
reg
from
Aire
KO
mice failed to attenuate the severity of multiorgan autoimmunity, demonstrating that their suppressive function is altered. Using bone marrow chimeras, we reveal that mTEC-specific expression of Aire controls the suppressive signature of recirculating T
reg
. Finally, mature mTEC lacking
Aire
were inefficient in stimulating peripheral T
reg
both in polyclonal and antigen-specific co-culture assays. Overall, this study demonstrates that Aire confers to mTEC the ability to restimulate recirculating T
reg
, unravelling a novel function for this master regulator in T
reg
biology.
Rift Valley fever (RVF) is a mosquito‐borne disease caused by the Rift Valley fever virus (RVFV). Rift Valley fever affects a large number of species, including human, and has severe impact on public ...health and the economy, especially in African countries. The present study examined the vector competence of three different European mosquito species, Culex pipiens (Linnaeus, 1758) form molestus (Diptera: Culicidae), Culex pipiens hybrid form and Stegomyia albopicta (= Aedes albopictus) (Skuse, 1894) (Diptera: Culicidae). Mosquitoes were artificially fed with blood containing RVFV. Infection, disseminated infection and transmission efficiency were evaluated. This is the first study to assess the transmission efficiency of European mosquito species using a virulent RVFV strain. The virus disseminated in Cx. pipiens hybrid form and in S. albopicta. Moreover, infectious viral particles were isolated from saliva of both species, showing their RVFV transmission capacity. The presence of competent Cx. pipiens and S. albopicta in Spain indicates that an autochthonous outbreak of RVF may occur if the virus is introduced. These findings provide information that will help health authorities to set up efficient entomological surveillance and RVFV vector control programmes.
Regulatory T lymphocytes expressing the transcription factor Foxp3 (Tregs) play an important role in the prevention of autoimmune diseases and other immunopathologies. Aberrations in Treg-mediated ...immunosuppression are therefore thought to be involved in the development of autoimmune pathologies, but few have been documented. Recent reports indicated a central role for Tregs developing during the neonatal period in the prevention of autoimmune pathology. We therefore investigated the development of Tregs in neonatal NOD mice, an important animal model for autoimmune type 1 diabetes. Surprisingly, we found that, as compared with seven other commonly studied inbred mouse strains, in neonatal NOD mice, exceptionally large proportions of developing Tregs express high levels of GITR and PD-1. The latter phenotype was previously associated with high Treg autoreactivity in C57BL/6 mice, which we here confirm for NOD animals. The proportions of newly developing GITR
PD-1
Tregs rapidly drop during the first week of age. A genome-wide genetic screen indicated the involvement of several diabetes susceptibility loci in this trait. Analysis of a congenic mouse strain confirmed that
contributes to the genetic control of GITR
PD-1
Treg development in neonates. Our data thus demonstrate an intriguing and paradoxical correlation between an idiosyncrasy in Treg development in NOD mice and their susceptibility to type 1 diabetes.
The present work was carried out to assess the effect of atmospheric ammonia (NH3) on soil physicochemical properties, soil enzymatic activities (β-glucosidase -β-GLU-, nitrate reductase –NR-, urease ...–UR-, protease –PRO-, acid phosphatase –PHO-, dehydrogenase –DHA-), soil microbial biomass and soil respiration. The study was conducted along a NH3 gradient in a Q. pubescens Milld. forest in the vicinity of two livestock farms. Because of NHy (NHy: NH3 and NH4+) deposition, N saturation was detected up to 330 m from the farms. This excess of N led to a decrease in soil C:N and an increase in soil nitrification processes, which resulted in an accumulation of the heavy N isotope (15N) in the soil. N saturation was also reflected in the activity of NR enzyme, which was inhibited. On the other hand, while UR enzyme was inhibited close to the farms possibly due to the high amount of N-NH4+ resulting from the hydrolysis of NH3, PRO activity was stimulated by the presence of organic nitrogen compounds and the need of soil organisms to meet the C demand. In addition, the activity of PHO and β-GLU enzymes was regulated by the relative amount of C and P that organisms need. Regarding biological variables, enhanced NH3 reduced soil microbial biomass and biomass respiratory efficiency. Finally, soil enzyme activities and soil microbial biomass have proved to be good biological indicators of soil quality.
•Enhanced NH3 deposition produced N saturation up to 330 m from the farms.•Under N saturation, nitrate reductase activity was inhibited.•Phosphatase and β-glucosidase activities were regulated by the need of C and P.•NH3 deposition reduced soil microbial biomass.
Development of Foxp3-expressing regulatory T-lymphocytes (Treg) in the thymus is controlled by signals delivered in T-cell precursors
via
the TCR, co-stimulatory receptors, and cytokine receptors. In ...absence of IL-2, IL-15 or their receptors, fewer Treg apparently develop in the thymus. However, it was recently shown that a substantial part of thymic Treg are cells that had recirculated from the periphery back to the thymus, troubling interpretation of these results. We therefore reassessed the involvement of IL-2 and IL-15 in the development of Treg, taking into account Treg-recirculation. At the age of three weeks, when in wt and IL-15-deficient (but not in IL-2-deficient) mice substantial amounts of recirculating Treg are present in the thymus, we found similarly reduced proportions of newly developed Treg in absence of IL-2 or IL-15, and in absence of both cytokines even less Treg developed. In neonates, when practically no recirculating Treg were found in the thymus, the absence of IL-2 led to substantially more reduced Treg-development than deficiency in IL-15. IL-2 but not IL-15 modulated the CD25, GITR, OX40, and CD73-phenotypes of the thymus-egress-competent and periphery-seeding Treg-population. Interestingly, IL-2 and IL-15 also modulated the TCR-repertoire expressed by developing Treg. Upon transfer into Treg-less
Foxp3
sf
mice, newly developed Treg from IL-2- (and to a much lesser extent IL-15-) deficient mice suppressed immunopathology less efficiently than wt Treg. Taken together, our results firmly establish important non-redundant quantitative and qualitative roles for IL-2 and, to a lesser extent, IL-15 in intrathymic Treg-development.
The emerging disease West Nile fever is caused by West Nile virus (WNV), one of the most widespread arboviruses. This study represents the first test of the vectorial competence of European Culex ...pipiens Linnaeus 1758 and Stegomyia albopicta (= Aedes albopictus) (both: Diptera: Culicidae) populations for lineage 1 and 2 WNV isolated in Europe. Culex pipiens and S. albopicta populations were susceptible to WNV infection, had disseminated infection, and were capable of transmitting both WNV lineages. This is the first WNV competence assay to maintain mosquito specimens under environmental conditions mimicking the field (day/night) conditions associated with the period of maximum expected WNV activity. The importance of environmental conditions is discussed and the issue of how previous experiments conducted in fixed high temperatures may have overestimated WNV vector competence results with respect to natural environmental conditions is analysed. The information presented should be useful to policymakers and public health authorities for establishing effective WNV surveillance and vector control programmes. This would improve preparedness to prevent future outbreaks.
In this work we have measured the molecular diffusion coefficient of the n-alkane binary series nCi-nC6, nCi-nC10, and nCi-nC12 at 298 K and 1 atm and a mass fraction of 0.5 by using the so-called ...sliding symmetric tubes technique. The results show that the diffusion coefficient at this concentration is proportional to the inverse viscosity of the mixture. In addition, we have also measured the diffusion coefficient of the systems nC12-nC6, nC12-nC7, and nC12-nC8 as a function of concentration. From the data obtained, it is shown that the diffusion coefficient of the n-alkane binary mixtures at any concentration can be calculated from the molecular weight of the components and the dynamic viscosity of the corresponding mixture at 50% mass fraction.
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