617 research outputs found

    IL-23 produced by CNS-resident cells controls T cell encephalitogenicity during the effector phase of experimental autoimmune encephalomyelitis

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    CNS-resident cells, in particular microglia and macrophages, are a source of inflammatory cytokines during inflammation within the CNS. Expression of IL-23, a recently discovered cytokine, has been shown to be critical for the development of experimental autoimmune encephalomyelitis (EAE) in mice. Expression of the p40 subunit of IL-12 and IL-23 by microglia has been shown in situ and in vitro, but direct evidence for a functional significance of p40 expression by CNS cells during an immune response in vivo is still lacking. Here we report that p40 plays a critical role in maintaining encephalitogenicity during the disease course. By using irradiation bone marrow chimeras, we have generated mice in which p40 is deleted from the CNS parenchyma but not the systemic immune compartment. Our studies show that p40 expressed by CNS-endogenous cells is critical for the development of myelin oligodendrocyte glycoprotein-induced EAE. In spite of the reduced clinical disease, the absence of p40 from the CNS has little impact on the degree of inflammation. Expression profiles of the CNS lesions show an increase in Th2 cytokines when compared with mice that develop EAE in the presence of CNS IL-12 and/or IL-23. Taken together, our data demonstrate that p40 expression by CNS-resident cells forms the basis for the Th1 bias of the CNS

    Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12

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    Experimental Autoimmune Encephalitis and Inflammation in the Absence of Interleukin-12

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    IL-12 is considered a critical proinflammatory cytokine for autoimmune diseases such as multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). IL-12 is a heterodimer composed of a p35 subunit and a common p40 subunit shared by other cytokines. Both IL-12 p40–/– and p35–/– mice fail to produce IL-12 p70 heterodimer. However, in contrast to p40–/– mice, p35–/– mice are highly susceptible to the induction of EAE, establishing that IL-12 p70 is not essential for the development of EAE. When compared with wild-type mice, both p40–/– and p35–/– mice show deficiencies in primary IFN-Îł responses by lymph node cells. Expression profiling of the inflamed CNS revealed that Th2 cytokines such as IL-4 and IL-10 are upregulated in p35–/– mice, whereas LT-α and TNF-α levels are reduced. These studies show that a molecule other than IL-12 p70, which uses the p40 subunit, fulfills the functions previously attributed to IL-12 with regard to the development and pathogenesis of this autoimmune disease

    First observation of medium-spin excitations in the 138Cs nucleus

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    Medium-spin, yrast excitations in the 138Cs nucleus, populated in the spontaneous fission of 248Cm, were observed for the first time. 138Cs was studied by means of prompt Îł-ray spectroscopy using the EUROGAM2 array. The newly observed yrast cascade, built on the known 6- isomer at 80 keV, was successfully described by shell model calculations. Analogously to the 136I isotone, the 6- isomer in 138Cs has the \ensuremath{(\pi g_{7/2} ^4 d_{5/2} \nu f_{7/2})_{6^-}} dominating configuration and the 7- excitation, located 175 keV above, corresponds to the \ensuremath{(\pi g_{7/2} ^3 d_{5/2}^2 \nu f_{7/2})_{7^-}} as dominating configuration. Similarly as in 136I, changing the position of the d 5/2 proton orbital improves the reproduction of the data. However, in 138Cs the energy of this orbital should be increased compared to its energy in 133Sb, to get the best description, in contrast to 136I and 135Sb, where it had to be decreased. The best reproduction of excitation energies in 138Cs is obtained assuming that the πd 5/2 orbital in 138Cs is located about 100 keV higher than in 133Sb. These observations suggest that the lowering of the d 5/2 s.p. energy in 135Sb is not a physical effect due to the appearance of a neutron skin, as proposed by other authors, but rather an artifact due to some deficiency of the input data used in the shell model calculations in the region of the doubly magic 132Sn core

    New Spins for ground states and isomers in 115^{115}Pd and 117^{117}Pd

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    Levels in 115Pd and 117Pd nuclei, populated in the spontaneous fission of 248Cm were studied by means of prompt gamma spectroscopy using the EUROGAM2 array of Anti-Compton spectrometers. Negative-parity, I = 9/2 excitations were identified, which are associated with the long-lived isomers in these nuclei, reported previously as 11/2- excitations. The new data indicate spin and parity 3/2 + for ground states in 115Pd and 117Pd instead of 5/2 + proposed in previous works. This result implicates changes of spin assignments to other levels in both nuclei

    Population overlap and habitat segregation in wintering Black-tailed Godwits Limosa limosa

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    Distinct breeding populations of migratory species may overlap both spatially and temporally, but differ in patterns of habitat use. This has important implications for population monitoring and conservation. To quantify the extent to which two distinct breeding populations of a migratory shorebird, the Black-tailed Godwit Limosa limosa, overlap spatially, temporally and in their use of different habitats during winter. We use mid-winter counts between 1990 and 2001 to identify the most important sites in Iberia for Black-tailed Godwits. Monthly surveys of estuarine mudflats and rice-fields at one major site, the Tejo estuary in Portugal in 2005-2007, together with detailed tracking of colour-ringed individuals, are used to explore patterns of habitat use and segregation of the Icelandic subspecies L. l. islandica and the nominate continental subspecies L. l. limosa. In the period 1990-2001, over 66 000 Black-tailed Godwits were counted on average in Iberia during mid-winter (January), of which 80% occurred at just four sites: Tejo and Sado lower basins in Portugal, and Coto Dontildeana and Ebro Delta in Spain. Icelandic Black-tailed Godwits are present throughout the winter and forage primarily in estuarine habitats. Continental Black-tailed Godwits are present from December to March and primarily use rice-fields. Iberia supports about 30% of the Icelandic population in winter and most of the continental population during spring passage. While the Icelandic population is currently increasing, the continental population is declining rapidly. Although the estuarine habitats used by Icelandic godwits are largely protected as Natura 2000 sites, the habitat segregation means that conservation actions for the decreasing numbers of continental godwits should focus on protection of rice-fields and re-establishment of freshwater wetlands
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