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1.
Front Immunol ; 15: 1358459, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38404576

RESUMO

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 GITRhighPD-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 Idd5 contributes to the genetic control of GITRhighPD-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.


Assuntos
Diabetes Mellitus Tipo 1 , Camundongos , Animais , Diabetes Mellitus Tipo 1/genética , Camundongos Endogâmicos NOD , Linfócitos T Reguladores , Receptor de Morte Celular Programada 1/genética , Camundongos Endogâmicos C57BL , Fatores de Transcrição
2.
Environ Sci Pollut Res Int ; 31(6): 9713-9731, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38194174

RESUMO

Indoor pollution and deposition dust (DD), in particular, are acquiring concern, due to long exposure time and importance of intake by humans through contact and ingestion. Hospitals look a special category of sites, owing to peculiar contaminants affecting them and to presence of people prone to adverse effects induced by toxicants. Four in-field campaigns aimed at understanding the chemical composition of DD were performed in five Italian hospitals. Measurements were performed before (autumn 2019), during (spring 2021), and after (winter 2022) the peak of SARS-CoV2 and when restrictions caused by pandemic were revoked (winter 2023). Parallel measurements were made outdoors (2022), as well as in a university and a dwelling. Targeted contaminants were n-alkanes and polycyclic aromatic hydrocarbons (PAHs), while iso- and anteiso-alkanes were analyzed to assess the impact of tobacco smoking. Total n-alkanes ranged from 3.9 ± 2.3 to 20.5 ± 4.2 mg/g, with higher percentages of short chain homologs in 2019. PAHs ranged from 0.24 ± 0.22 to 0.83 ± 0.50 mg/g, with light congeners (≤ 228 a.m.u.) always exceeding the heavy ones (≥ 252 a.m.u.). According to carbon preference indexes, alkanes originated overall from anthropogenic sources. Microorganisms resulted to affect a hospital, and tobacco smoke accounted for ~ 4-20‰ of DD mass. As for PAH sources, the diagnostic concentration ratios suggested the concourse of biological matter burning and vehicle emission. Benzo[a]pyrene equivalent carcinogenic and mutagenic potencies of depositions at hospitals ranged ~ 9-39 µg/g and ~ 15-76 µg/g, respectively, which seems of concern for health. DD composition in hospitals was different from that outside the premises, as well as that found at university and at dwelling.


Assuntos
COVID-19 , Hidrocarbonetos Policíclicos Aromáticos , Humanos , Hidrocarbonetos Policíclicos Aromáticos/análise , Alcanos/análise , Monitoramento Ambiental/métodos , RNA Viral , Pandemias , SARS-CoV-2 , Substâncias Perigosas , Poeira
3.
Front Immunol ; 13: 965303, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36159793

RESUMO

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 Foxp3sf 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.


Assuntos
Interleucina-2 , Linfócitos T Reguladores , Animais , Citocinas , Fatores de Transcrição Forkhead/genética , Camundongos , Receptores de Antígenos de Linfócitos T
4.
Environ Sci Pollut Res Int ; 29(44): 65904-65923, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35876994

RESUMO

Chemical signature of airborne particulates and deposition dusts is subject of study since decades. Usually, three complementary composition markers are investigated, namely, (i) specific organic compounds; (ii) concentration ratios between congeners, and (iii) percent distributions of homologs. Due to its intrinsic limits (e.g., variability depending on decomposition and gas/particle equilibrium), the identification of pollution sources based on molecular signatures results overall restricted to qualitative purposes. Nevertheless, chemical fingerprints allow drawing preliminary information, suitable for successfully approaching multivariate analysis and valuing the relative importance of sources. Here, the state-of-the-art is presented about the molecular fingerprints of non-polar aliphatic, polyaromatic (PAHs, nitro-PAHs), and polar (fatty acids, organic halides, polysaccharides) compounds in emissions. Special concern was addressed to alkenes and alkanes with carbon numbers ranging from 12 to 23 and ≥ 24, which displayed distinct relative abundances in petrol-derived spills and exhausts, emissions from microorganisms, high vegetation, and sediments. Long-chain alkanes associated with tobacco smoke were characterized by a peculiar iso/anteiso/normal homolog fingerprint and by n-hentriacontane percentages higher than elsewhere. Several concentration ratios of PAHs were identified as diagnostic of the type of emission, and the sources of uncertainty were elucidated. Despite extensive investigations conducted so far, the origin of uncommon molecular fingerprints, e.g., alkane/alkene relationships in deposition dusts and airborne particles, remains quite unclear. Polar organics resulted scarcely investigated for pollution apportioning purposes, though they looked as indicative of the nature of sources. Finally, the role of humans and living organisms as actual emitters of chemicals seems to need concern in the future.


Assuntos
Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Poluição por Fumaça de Tabaco , Poluentes Atmosféricos/análise , Alcanos/análise , Alcenos/análise , Carbono/análise , Poeira/análise , Monitoramento Ambiental/métodos , Ácidos Graxos/análise , Humanos , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluição por Fumaça de Tabaco/análise
5.
Environ Sci Pollut Res Int ; 29(28): 43048-43057, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35092585

RESUMO

Tobacco smoke (TS) is the source of a number of toxicants affecting the atmosphere and poses a threat to smokers and the whole community. Chemical, physical, and toxicological features of smoking products (vapors as well as mainstream, side stream, and third-hand smoke) have been investigated extensively. Special attention is paid to organic compounds (individually or in combination giving rise to peculiar molecular fingerprints), potentially able to act as "chemical signature" of TS. In this regard, the percent distribution of long-chainnormal, iso, and anteiso alkanes was ascertained as typical of TS. Nevertheless, until now no indexes have been identified as suitable for assessing the global TS contribution to environmental pollution, e.g., the TS percentage in carbonaceous aerosol and in deposited dusts, the only exception consisting in the use of nicotelline as tracer. This paper describes the results of an extensive study aimed at chemically characterizing the nonpolar lipid fraction associated to suspended particulates (PMs) and deposition dusts (DDs) collected at indoor and outdoor locations. Based on the iso, anteiso, and normal C29-C34 alkane profile in the samples as well in tobacco smoke- and no-TS-related emissions (literature data), various parameters describing the distribution of compounds were investigated. Finally, a cumulative variable was identified as the tobacco smoke impact index (TS%) suitable for estimating the TS percentage occurring in the particulate matter. The TS% rates were plotted vs. the exceedance of normal C31 alkane with respect to the average of C29 and C33 homologs, which results higher in TS than in most other emissions, revealing a link in the case of suspended particulates but not of deposited dusts. According to back analysis carried out on all particulate matter sets, it was found that traces of TS affect even remote areas, while inside the smokers' homes the contributions of TS to PM could account for up to ~61% and ~10%, respectively, in PM and DD. This confirms the need of valuing the health risk posed by TS to humans, by means of tools easy to apply in extensive investigations.


Assuntos
Poluição do Ar em Ambientes Fechados , Poluição por Fumaça de Tabaco , Poluição do Ar em Ambientes Fechados/análise , Alcanos/análise , Poeira/análise , Monitoramento Ambiental/métodos , Humanos , Material Particulado/análise , Poluição por Fumaça de Tabaco/análise
6.
Int J Mol Sci ; 22(20)2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34681684

RESUMO

Adenomatous polyps are precancerous lesions associated with a higher risk of colorectal cancer (CRC). Curcumin and anthocyanins have shown promising CRC-preventive activity in preclinical and epidemiological studies. The objective of this window-of-opportunity, proof-of principle trial was to evaluate the effect of curcumin combined with anthocyanin supplements on tissue biomarkers of colorectal adenomatous polyps. Eligible patients received either anthocyanin and curcumin supplementation or related matching placebo for 4-6 weeks before polyp removal. Adenomatous polyps and adjacent tissue biopsies were collected at baseline and after supplementation for immunohistochemical assessment of ß-catenin, NF-kappa B (NF-κB), Ki-67, P53, and dysplasia. No differences were observed in baseline biomarker expression between normal and dysplastic tissues. The combination of anthocyanins and curcumin resulted in a significant borderline reduction of NF-κB immunohistochemistry (IHC) expression in adenoma tissue (geometric mean ratio (GMR): 0.72; 95% confidence interval (CI): 0.51-1.00; p-value: 0.05) and a trend to a reduction of Ki-67 (GMR: 0.73; 95% CI: 0.50-1.08; p-value: 0.11). No significant modulation of biomarkers in normal adjacent mucosa was observed. We concluded that the combined supplementation of anthocyanins and curcumin seems to lead to a potentially favorable modulation of tissue biomarkers of inflammation and proliferation in colon adenomas.


Assuntos
Pólipos Adenomatosos/prevenção & controle , Antocianinas/farmacologia , Neoplasias Colorretais/prevenção & controle , Curcumina/farmacologia , Suplementos Nutricionais , Pólipos Adenomatosos/genética , Pólipos Adenomatosos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Antígeno Ki-67/genética , Masculino , Pessoa de Meia-Idade , NF-kappa B/genética , Proteína Supressora de Tumor p53/genética
7.
Diabetes ; 70(8): 1729-1737, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34035042

RESUMO

Regulatory T lymphocytes expressing the forkhead/winged helix transcription factor Foxp3 (Treg) play a vital role in the protection of the organism from autoimmune disease and other immunopathologies. The antigen specificity of Treg plays an important role in their in vivo activity. We therefore assessed the diversity of the T-cell receptors (TCRs) for antigen expressed by Treg newly developed in the thymus of autoimmune type 1 diabetes-prone NOD mice and compared it to the control mouse strain C57BL/6. Our results demonstrate that use of the TCRα and TCRß variable (V) and joining (J) segments, length of the complementarity determining region (CDR) 3, and the diversity of the TCRα and TCRß chains are comparable between NOD and C57BL/6 mice. Genetic defects affecting the diversity of the TCR expressed by newly developed Treg therefore do not appear to be involved in the etiology of type 1 diabetes in the NOD mouse.


Assuntos
Diabetes Mellitus Tipo 1/patologia , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T Reguladores/patologia , Timo/patologia , Animais , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Transgênicos , Linfócitos T Reguladores/imunologia , Timo/imunologia
8.
Air Qual Atmos Health ; 14(9): 1375-1391, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33880133

RESUMO

Size distribution of toxicants in airborne particulates remains insufficiently investigated in Algeria. A 1-year campaign was performed at Bab Ezzouar, Algiers (Algeria), aimed at characterizing particulates for their physical and chemical features. For this purpose, scanning electronic microscopy (SEM), Raman spectroscopy (RaS), and GC-MS methodologies were applied. The samples were collected on daily basis by means of a high-volume sampling (HVS) system equipped with cascade impactor separating three size fractions, i.e., particles with aerodynamic diameters d < 1.0 µm (PM1), 1.0 µm

10.
Eur J Immunol ; 51(3): 580-593, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32730634

RESUMO

Regulatory T lymphocytes (Treg) play a vital role in the protection of the organism against autoimmune pathology. It is therefore paradoxical that comparatively large numbers of Treg were found in the thymus of type I diabetes-prone NOD mice. The Treg population in the thymus is composed of newly developing cells and cells that had recirculated from the periphery back to the thymus. We here demonstrate that exceptionally large numbers of Treg develop in the thymus of young, but not adult, NOD mice. Once emigrated from the thymus, an unusually large proportion of these Treg is activated in the periphery, which causes a particularly abundant accumulation of recirculating Treg in the thymus. These cells then rapidly inhibit de novo development of Treg. The proportions of developing Treg thus reach levels similar to or lower than those found in most other, type 1 diabetes-resistant, inbred mouse strains. Thus, in adult NOD mice the particularly large Treg-niche is actually composed of mostly recirculating cells and only few newly developing Treg.


Assuntos
Linfócitos T Reguladores/imunologia , Timo/imunologia , Animais , Diabetes Mellitus Tipo 1/imunologia , Tolerância Imunológica/imunologia , Masculino , Camundongos , Camundongos Endogâmicos NOD
11.
Immunity ; 50(3): 629-644.e8, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30737147

RESUMO

Upon activation, naive CD4+ T cells differentiate into distinct T cell subsets via processes reliant on epigenetically regulated, lineage-specific developmental programs. Here, we examined the function of the histone methyltransferase SETDB1 in T helper (Th) cell differentiation. Setdb1-/- naive CD4+ T cells exhibited exacerbated Th1 priming, and when exposed to a Th1-instructive signal, Setdb1-/- Th2 cells crossed lineage boundaries and acquired a Th1 phenotype. SETDB1 did not directly control Th1 gene promoter activity but relied instead on deposition of the repressive H3K9me3 mark at a restricted and cell-type-specific set of endogenous retroviruses (ERVs) located in the vicinity of genes involved in immune processes. Refined bioinformatic analyses suggest that these retrotransposons regulate Th1 gene cis-regulatory elements or act as Th1 gene enhancers. Thus, H3K9me3 deposition by SETDB1 ensures Th cell lineage integrity by repressing a repertoire of ERVs that have been exapted into cis-regulatory modules to shape and control the Th1 gene network.


Assuntos
Linhagem da Célula/imunologia , Retrovirus Endógenos/imunologia , Histona Metiltransferases/imunologia , Histona-Lisina N-Metiltransferase/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Diferenciação Celular/imunologia , Feminino , Histonas/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas/imunologia , Células Th1/imunologia , Células Th2/imunologia
12.
Environ Pollut ; 248: 145-158, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30784833

RESUMO

A scientific campaign was undertaken along the Western sector of the Mediterranean Sea in the summer 2015 (26th Jun to 13th Jul), with the goal of gathering information about organic contaminants affecting marine aerosol over the Italian seas and with a special focus on changes in composition due to sources. 24 PM10 atmospheric samples in total were chemically characterized, including polycyclic aromatic hydrocarbons (PAHs), aliphatic hydrocarbons (n-alkanes) and phthalate esters. Contemporarily, regulated gaseous toxicants (i.e. ozone, nitrogen oxides and sulfur dioxide) and meteorological parameters were recorded. Samplings were carried out inshore in front of harbors (N = 7) and along the cruise, both during the vessel shipping (N = 11, transects) and at its stops offshore (N = 6). Total PAH concentrations ranged from 0.03 to 1.94 ng/m3 and raised close to harbors and coastal sites, confirming that continental sources were responsible for the strong increase of pollution levels there compared to offshore. The percent composition and diagnostic ratio rates of PAHs were different for harbors, while transects were in agreement with offshore stops, possibly due to the different impact of pollution sources. n-Alkanes (C21C38) and the corresponding carbon preference index rates (CPI) were assessed; their values ranged 8.7-90 ng/m3 and 1.1-2.9 respectively, which suggested that fossil fuel combustion was the dominant source, though biogenic emission could contribute. Alkyl phthalates revealed wide variability in concentrations among aerosol samples. Moreover, long-range atmospheric transport and particle ageing effect induced by photo-oxidants were important factors controlling the composition of organic aerosols in the Mediterranean Sea air.


Assuntos
Aerossóis/análise , Poluentes Atmosféricos/análise , Alcanos/análise , Monitoramento Ambiental/métodos , Ácidos Ftálicos/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Mar Mediterrâneo , Estações do Ano , Água do Mar/química
13.
Immunol Lett ; 204: 9-15, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30308217

RESUMO

Hematopoietic precursors entering the thymus undergo a maturation process leading to the generation of a variety of T cell subsets that migrate to the periphery to perform their effector functions. This maturation process is strictly regulated by multiple interactions of developing T cells with thymic stroma cells. Signals received via the T cell receptor for antigen, co-stimulatory molecules and cytokines will determine, through thymic selection and lineage choice, thymocyte-fate. Recently, different populations of peripheral antigen presenting cells and T cells have been reported to enter the thymus. Here we review how these cells migrating from the periphery to the thymus modulate T cell development.


Assuntos
Células Apresentadoras de Antígenos/citologia , Células Apresentadoras de Antígenos/imunologia , Diferenciação Celular/imunologia , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/imunologia , Timo/citologia , Timo/imunologia , Animais , Células Apresentadoras de Antígenos/metabolismo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Movimento Celular/imunologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Humanos , Tolerância Imunológica , Subpopulações de Linfócitos T/metabolismo , Timócitos/citologia , Timócitos/imunologia , Timócitos/metabolismo , Timo/metabolismo
14.
Chemosphere ; 200: 106-115, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29476955

RESUMO

Laboratory and field studies were carried out to assess the effects of oxidative degradation and volatilization on PM10 bound polycyclic aromatic hydrocarbons (PAHs), collected at low volume condition according to the EU sampling reference method EN12341:2014 (flow rate 2.3 m3 h-1), on 47 mm quartz filters. For the laboratory experiments, pairs of twin samples were collected in field and, after treatments favoring decomposition or/and volatilization of PAHs on one sample, the PAH amount was compared with that of the corresponding untreated sample. Ozone exposure caused a general PAHs decay with more marked effects on benzo [a]pyrene, perylene and benz [a]anthracene; these compounds showed, similarly to benzo [ghi]perylene, correlations between ozone dose and losses. Treatments with zero air exhibited losses due to volatilization even for 5-ring PAHs up to benzo [a]pyrene, whereas a linear dependence was observed between filter PAH load and losses for benzo [a]anthracene, chrysene and benzofluoranthenes. Concentrations on samples collected simultaneously over 48, 24, 12 and 6 h were compared. Results confirmed a lack of temporal auto-consistency in the PAHs sampling methodology here adopted. In particular higher atmospheric PAH concentrations were ascertained on samples constituted by cumulative filters exposed over shorter sampling times. When 24-h and 2 × 12-h samples were compared, comparable losses were evaluated in the hot and cold seasons. This finding shows that, although in summer meteorology conditions favor sampling artifacts, the effectiveness of these phenomena continue in the winter, probably due to the larger amount of PAH available on the sampling filter (total PAHs ∼ 10 vs 0.5 ng m-3).


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Laboratórios , Estresse Oxidativo , Material Particulado/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/análise , Manejo de Espécimes , Poluentes Atmosféricos/química , Poluentes Atmosféricos/metabolismo , Poluição do Ar/prevenção & controle , Artefatos , Material Particulado/química , Hidrocarbonetos Policíclicos Aromáticos/química , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Volatilização
15.
Gerontology ; 64(1): 28-35, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28704827

RESUMO

The generation and function of immuno-suppressive regulatory T lymphocytes (Treg), which can differentiate in the thymus (tTreg) or in the periphery (pTreg), are regulated in an age-dependent manner. tTreg are produced at high levels in the first weeks of age, when they expand and colonize secondary lymphoid organs and peripheral tissues to protect the organism from autoimmune diseases and to promote tissue repair. Once this population of Treg is operational in the periphery, at puberty, thymic output of Treg declines, but self-reactive tTreg generated early on in life are maintained over time and play a major role in preserving homeostasis of the immune system. Extra-thymic pTreg differentiation declines later on in life. pTreg generated throughout life mainly protect the organism from chronic inflammation and the semi-allogeneic fetus from rejection. In this review, age-dependent modulation of the production and function of these two populations of Treg is described.


Assuntos
Envelhecimento/imunologia , Linfócitos T Reguladores/imunologia , Envelhecimento/patologia , Animais , Diferenciação Celular/imunologia , Proliferação de Células , Homeostase/imunologia , Humanos , Tecido Linfoide/citologia , Tecido Linfoide/imunologia , Camundongos , Tolerância a Antígenos Próprios/imunologia , Linfócitos T Reguladores/classificação , Linfócitos T Reguladores/citologia , Timo/citologia , Timo/imunologia
16.
Protein Cell ; 9(4): 322-332, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28540653

RESUMO

Immunosuppressive regulatory T lymphocytes (Treg) expressing the transcription factor Foxp3 play a vital role in the maintenance of tolerance of the immune-system to self and innocuous non-self. Most Treg that are critical for the maintenance of tolerance to self, develop as an independent T-cell lineage from common T cell precursors in the thymus. In this organ, their differentiation requires signals from the T cell receptor for antigen, from co-stimulatory molecules, as well as from cytokine-receptors. Here we focus on the cytokines implicated in thymic development of Treg, with a particular emphasis on the roles of interleukin-2 (IL-2) and IL-15. The more recently appreciated involvement of TGF-ß in thymic Treg development is also briefly discussed. Finally, we discuss how cytokine-dependence of Treg development allows for temporal, quantitative, and potentially qualitative modulation of this process.


Assuntos
Fatores de Transcrição Forkhead/genética , Interleucina-15/genética , Interleucina-2/genética , Animais , Diferenciação Celular/genética , Citocinas/imunologia , Fatores de Transcrição Forkhead/imunologia , Regulação da Expressão Gênica , Tolerância Imunológica/genética , Interleucina-15/imunologia , Interleucina-2/imunologia , Camundongos , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/imunologia
17.
Chemosphere ; 189: 330-339, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28942259

RESUMO

The artifacts induced by oxidative degradation and volatilization were assessed with regards to determination of particulate atmospheric PAHs collected at low volume conditions (2.3 m3 h-1) according to the EU Reference Method EN 12341:2014. In order to evaluate the oxidative degradation, PAH measures carried out through collecting airborne particulate with and without ozone denuders were examined. Simultaneously, the influence of volatilization was investigated by comparing concentrations of PAHs in particulate samples collected over 24-h and 12-h using conventional instruments. Summer and winter/spring campaigns were carried out in order to assess the influence of environmental contour on the artifact processes. Oxidative degradation led to a general decrease of PAH concentrations in both periods; in particular, the highest losses were observed for benzo[a]pyrene and perylene reaching, in average, ca. 20%. In the summer, the effect of volatilization exceeded that of oxidative degradation for light PAHs up to benzo[e]pyrene. In the winter/spring time, the influence of both artifact typologies could be mitigated by splitting the normal 24-h collection interval starting at midnight into two 12-h intervals. A mitigation of the losses could even be obtained by fixing the start time sampling fixed at noon or in the first hours of the day. Finally, the feasibility of collecting PAHs through prolonged sampling (>1 month) at the flow rate of 1.1 L min-1 was preliminarily investigated. Results indicated that this approach is unsuitable for minimizing the oxidative artifacts.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , Monitoramento Ambiental , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluição do Ar/prevenção & controle , Artefatos , Benzo(a)pireno , Oxirredução , Ozônio , Estações do Ano , Manejo de Espécimes , Volatilização
18.
Environ Sci Pollut Res Int ; 24(32): 25260-25275, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28929369

RESUMO

Particulate polycyclic aromatic hydrocarbons (PAHs), n-alkanes, and gaseous pollutants were collected from the harbor and the urban area of Crotone (Southern Italy) in October 2015. The atmospheric concentrations of organic substances associated to PM10 were determined daily, while gaseous pollutants (BTEX, O3, SO2, NOx, NO2, and NH3) were monitored on monthly basis by means of diffusive sampling. Total PAHs reached, on the average, 1.56 ± 0.72, 0.33 ± 0.14, and 0.59 ± 0.37 ng/m3 at the urban monitoring stations (Fiore, Fermi) and at the harbor, respectively. The percent distribution and diagnostic concentration ratios of PAHs were similar at Fermi and harbor, whereas differences were found through comparison with Fiore site. Biogenic n-alkanes (n-C29, and n-C31) were the most abundant components, indicating the important impact of terrestrial higher plants in all sites. On the other hand, n-C23-n-C25 homologs originated from incomplete combustion of fossil fuel were not negligible (CPI2.5 = 2.4) in harbor, confirming the role of anthropogenic sources there. Inside the harbor, SO2 concentrations ranged from 5.6 to 14.8 µg/m3 showing the maximum value within the old part of the harbor (touristic port). A statistical significant difference between the harbor and the surroundings was indeed observed for this pollutant, which is a specific marker of ship emissions. The other gaseous species monitored did not exhibit the same distribution, with exception of NH3 and benzene, whose concentration values ranged from 2.8 to 6.9 µg/m3 and 0.3 to 1.4 µg/m3, respectively, and peaked at the same harbor site. Similarities were found in NOx, NO2, and O3 concentration distributions, showing high values in the New Port area.


Assuntos
Poluição do Ar , Monitoramento Ambiental , Poluentes Atmosféricos/análise , Alcanos/análise , Itália , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Estações do Ano
19.
Environ Sci Pollut Res Int ; 24(26): 21256-21261, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28736802

RESUMO

Psychotropic substances (PSs) are known to affect air and waters, while scarce attention has been paid to their occurrence in settled dusts although they can reach important concentrations there; moreover, no procedures have been developed for this specific purpose. In this study, a list of PSs (i.e., nicotine, cotinine, caffeine, cocaine, cannabinol, Δ9-tetrahydrocannabinol, cannabidiol, amphetamine, heroin, and methadone) were characterized in dusts from Rome and Fiumicino international airport, Italy, and from Ouargla city, Algeria. The analytical procedure, based on ultra-sonic bath extraction, silica column chromatography, and GC-MSD analysis, provided good recovery, uncertainty, sensitivity, and lack of interferences for all substances except amphetamine. In NIST SRM-2585 house dust, nicotine, cotinine, caffeine, cocaine, and cannabinol accounted for ~5.95, 0.87, 4.17, 7.0, and 2.2 µg/g, respectively; on the other hand, methadone, tetrahydrocannabinol, cannabidiol, and heroin (all <0.025 µg/g) were below the detection limit of the method. Two sites at the Fiumicino airport were affected by different loads of PSs (e.g., 0.76 and 2.80 ng/m2 of cocaine). In Ouargla, where dust was collected in a primary school and a dwelling, nicotine ranged from ~60 ± 50 to ~86 ± 89 ng/m2, cocaine was absent, and cannabinoids (0.35 ± 0.43 ng/m2 as total) were found only in the home. In Rome, nicotine, caffeine, cocaine, and cannabinol reached ca. 700, 1470, 0.82, and 2.4 ng/m2, respectively, in a smokers' home, but they were ca. 1300, 25,000, 670, and 1700 ng/m2 in a non-smoker home. In conclusion, all dusts revealed the presence of illicit PSs. Further studies are necessary to understand the links between the PS amounts in airborne particulates and in dusts, as well as the PS origin and fate in interiors.


Assuntos
Poluentes Atmosféricos/análise , Poeira/análise , Psicotrópicos/análise , Argélia , Cidades , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Cidade de Roma
20.
Chemosphere ; 183: 62-68, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28535462

RESUMO

Till now, no attention has been paid to pharmaceuticals (PCs) in the air, though they are known to affect waters, soils, foods and biota. This paper describes the first attempt to characterize the PC occurrence in the air. Airborne particulates (PM10 or PM2.5 fractions, from Amsterdam, Netherland, Rome and Rende, Italy) were sampled on quartz fiber filter by means of pumping systems operating at medium-volume conditions (16 or 38.5 L min-1). The samples were solvent extracted through sonication with a dichloromethane:acetone:methanol mixture and reduced close to dryness; three fractions of the residue were separated through column chromatography; they comprised non polar, low polar and very polar organic compounds, respectively, and PCs were in the third one. Chemical analysis was performed by means of gas chromatography coupled with mass spectrometric detection (GC-MSD), after treatment of solutions with methyl,tertzbutylsilyl-trifluoroacetamide (MTBSTFA) to form silyl derivatives of most PCs. The following substances were investigated: acetaminophenol, ibuprofen, ketoprofen, fenoprefen, naproxen, fenofibrate, diclofenac, acetylcysteine and sulfanilamide; p-hydroxybenzoic acid and salicylic acid; and parabens (methyl, ethyl and propyl). Except aspirin, acetamidophenol, acetylcysteine and sulfanilamide, the target compounds could be quantified with good repeatability, reproducibility and percent recoveries (on the average, ∼7.5%, ∼7.1% and 91%, respectively). The PC concentrations ranged <0.1-8.6 ng m-3; season dependent drug profiles could be observed in Rome and Rende.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Material Particulado/química , Preparações Farmacêuticas/análise , Poluentes Atmosféricos/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Itália , Países Baixos , Tamanho da Partícula , Preparações Farmacêuticas/química , Reprodutibilidade dos Testes , Estações do Ano
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