RESUMEN
Helminthic infections modulate host immunity and may protect their hosts from developing immunological diseases like inflammatory bowel disease. Induction of regulatory T cells (Tregs) may be an important part of this protective process. Heligmosomoides polygyrus bakeri infection also promotes the production of the regulatory cytokines TGF-ß and IL-10 in the gut. In the intestines, TGF-ß helps induce regulatory T cells. This study used Foxp3/IL-10 double reporter mice to investigate the effect of TGF-ß on the differentiation of colon and mesenteric lymph node-derived murine Foxp3- IL-10- CD4+ T cells into their regulatory phenotypes. Foxp3- IL-10- CD4+ T cells from H. polygyrus bakeri-infected mice, as opposed to T cells from uninfected animals, cultured in vitro with TGF-ß and anti-CD3/CD28 mAb differentiated into Foxp3+ and/or IL-10+ T cells. The IL-10-producing T cells nearly all displayed CD25. Smad7 is a natural inhibitor of TGF-ß signaling. In contrast to gut T cells from uninfected mice, Foxp3- IL10- CD4+ T cells from H. polygyrus bakeri-infected mice displayed reduced Smad7 expression and responded to TGF-ß with Smad2/3 phosphorylation. The TGF-ß-induced Tregs that express IL-10 blocked colitis when transferred into the Rag/CD25- CD4+ T cell transfer model of inflammatory bowel disease. TGF-ß had a greatly diminished capacity to induce Tregs in H. polygyrus bakeri-infected transgenic mice with constitutively high T cell-specific Smad7 expression. Thus, infection with H. polygyrus bakeri causes down-modulation in Smad7 expression in intestinal CD4+ T cells, which allows the TGF-ß produced in response to the infection to induce the Tregs that prevent colitis.
Asunto(s)
Colitis/inmunología , Interleucina-10/inmunología , Nematospiroides dubius/inmunología , Proteína smad7/inmunología , Infecciones por Strongylida/inmunología , Linfocitos T Reguladores/inmunología , Factor de Crecimiento Transformador beta/inmunología , Animales , Colitis/patología , Colitis/prevención & control , Interleucina-10/genética , Ratones , Ratones Transgénicos , Proteína smad7/genética , Infecciones por Strongylida/genética , Infecciones por Strongylida/patología , Linfocitos T Reguladores/patología , Factor de Crecimiento Transformador beta/genéticaRESUMEN
A series of tri-tert-butyl zinc(II) phthalocyanines (Pcs) substituted with pyridyl, carboxyl, or picolinic acid anchoring groups on the periphery were prepared. Photovoltaic (PV) studies on these dyes were carried out revealing some interesting features. In the case of the pyridyl-substituted Pcs, the PV properties were found to depend strongly on the the pyridyl substitution pattern (meta or para) and the number of pyridyl units at the macrocycle's periphery (one or two). For these four pyridyl-substituted Pcs, higher photovoltaic efficiencies were obtained for 1)â the para- versus the meta-substituted Pcs, and 2)â the mono- versus the bis-functionalized dyes. In order to improve the poor adsorption of the pyridyl-substituted Pcs onto TiO2 , a new dye was tested bearing a picolinic acid unit. This moiety combines a carboxylic acid function, as a strong anchoring group for binding to TiO2 , with an electron-withdrawing nitrogen atom for better electron injection into the semiconductor's conduction band. For this latter system, an improvement in the PV efficiency up to 2.1 % was obtained.
RESUMEN
Helminthic infections modulate host immunity and may protect people in less-developed countries from developing immunological diseases. In a murine colitis model, the helminth Heligmosomoides polygyrus bakeri prevents colitis via induction of regulatory dendritic cells (DCs). The mechanism driving the development of these regulatory DCs is unexplored. There is decreased expression of the intracellular signaling pathway spleen tyrosine kinase (Syk) in intestinal DCs from H. polygyrus bakeri-infected mice. To explore the importance of this observation, it was shown that intestinal DCs from DC-specific Syk(-/-) mice were powerful inhibitors of murine colitis, suggesting that loss of Syk was sufficient to convert these cells into their regulatory phenotype. DCs sense gut flora and damaged epithelium via expression of C-type lectin receptors, many of which signal through the Syk signaling pathway. It was observed that gut DCs express mRNA encoding for C-type lectin (CLEC) 7A, CLEC9A, CLEC12A, and CLEC4N. H. polygyrus bakeri infection downmodulated CLEC mRNA expression in these cells. Focusing on CLEC7A, which encodes for the dectin-1 receptor, flow analysis showed that H. polygyrus bakeri decreases dectin-1 expression on the intestinal DC subsets that drive Th1/Th17 development. DCs become unresponsive to the dectin-1 agonist curdlan and fail to phosphorylate Syk after agonist stimulation. Soluble worm products can block CLEC7A and Syk mRNA expression in gut DCs from uninfected mice after a brief in vitro exposure. Thus, downmodulation of Syk expression and phosphorylation in intestinal DCs could be important mechanisms through which helminths induce regulatory DCs that limit colitis.
Asunto(s)
Colitis/prevención & control , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Intestinos/citología , Transducción de Señal , Quinasa Syk/metabolismo , Animales , Colitis/inmunología , Colitis/parasitología , Modelos Animales de Enfermedad , Intestinos/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Nematospiroides dubius/inmunología , ARN Mensajero/genética , ARN Mensajero/inmunología , Infecciones por Strongylida/inmunología , Infecciones por Strongylida/parasitología , Quinasa Syk/deficiencia , Quinasa Syk/genéticaRESUMEN
A series of eight Ru(ii) heteroleptic complexes incorporating an ancillary [2,2']bipyridine functionalised at the [4,4'] positions with one (-type) or two (-type) thienylenevinylenes (nTVs, n = 2 or 4) is reported. Three types of substitutions have been used for nTVs: hexylthioether, hexyloxy and hexyl. The characterisation of the half-sandwich intermediates and final complexes is provided. In particular, the half-sandwich complexes in the -type series are obtained as a racemate, whereas the heteroleptic complexes consist of two regioisomers. Finally, these complexes have been tested as dyes in dye-sensitized solar cells (DSSCs). Counterintuitively, better performances were obtained for -type complexes with shorter 2TV moieties. The best performing dye was the Ru(ii) complex mono-functionalized with a 2TV moiety having an hexylthioether substitution (), which achieved a maximum power efficiency of 2.77% under full sun illumination (AM1.5G standard conditions). The structure-performance relationship in DSSCs is discussed based on photovoltaic and electrochemical data and DFT-calculations.
RESUMEN
The detailed synthesis and characterization of four ruthenium(II) complexes [RuLL'(NCS)2 ] is reported, in which L represents a 2,2'-bipyridine ligand functionalized at the 4,4' positions with benzo[1,2-b:4,5-b']dithiophene derivatives (BDT) and L' is 2,2'-bipyridine-4,4'-dicarboxylic acid unit (dcbpy) (NCS=isothiocyanate). The reaction conditions were adapted and optimized for the preparation of these amphiphilic complexes with a strong lipophilic character. The photovoltaic performances of these complexes were tested in TiO2 dye-sensitized solar cell (DSSC) achieving efficiencies in the range of 3-4.5 % under simulated one sun illumination (AM1.5G).
RESUMEN
In this work, we report the use of bulky substitutions in a new heteroleptic ruthenium(II) bipyridine complex, Ru(NCS)2LL', coded TT-230 to obtain high open-circuit potential in a dye-sensitized solar cell (where L is a bipyridine ligand appended with two cyclopenta(2,1-b;3,4-bA)dithiophene moieties, and L' = 4,4,'-dicarboxylic acid 2,2'-bipyridine). The electrolytes based on cobalt complexes have shown significant advantages in terms of attainable open-circuit potential compared to the standard iodide/tri-iodide redox mediators. These merits of the cobalt complexes were previously realized with a porphyrin sensitizer, achieving a VOC greater than 1 V in DSC. However, with conventional Ru(II)-polypyridyl complexes such as the C101 dye, similar increase in the VOC could not be attained due to the enhanced recombination. In this work, we have shown that the use of bulky substituents can prevent the back reaction of photogenerated electron and subsequently increase the open-circuit potential of the device. The recombination processes were investigated by transient photovoltage decay measurements.