Functional Interleukin-17 Receptor A is Expressed in Central Nervous System Glia and Upregulated in Experimental Autoimmune Encephalomyelitis

Background: Interleukin-17A (IL-17A) is the founding member of a novel family of inflammatory cytokines that plays a critical role in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). IL-17A signals through its receptor, IL-17RA, which is expressed in many peripheral tissues; however, expression of IL-17RA in the central nervous system (CNS) and its role in CNS inflammation are not well understood. Methods: EAE was induced in C57Bl/6 mice by immunization with myelin oligodendroglial glycoprotein. IL-17RA expression in the CNS was compared between control and EAE mice using RT-PCR, in situ hybridization, and immunohistochemistry. Cell-type specific expression was examined in isolated astrocytic and microglial cell cultures. Cytokine and chemokine production was measured in IL-17A treated cultures to evaluate the functional status of IL-17RA. Results: Here we report increased IL-17RA expression in the CNS of mice with EAE, and constitutive expression of functional IL-17RA in mouse CNS tissue. Specifically, astrocytes and microglia express IL-17RA in vitro, and IL-17A treatment induces biological responses in these cells, including significant upregulation of MCP-1, MCP-5, MIP-2 and KC chemokine secretion. Exogenous IL-17A does not significantly alter the expression of IL-17RA in glial cells, suggesting that upregulation of chemokines by glial cells is due to IL-17A signaling through constitutively expressed IL-17RA. Conclusion: IL-17RA expression is significantly increased in the CNS of mice with EAE compared to healthy mice, suggesting that IL-17RA signaling in glial cells can play an important role in autoimmune inflammation of the CNS and may be a potential pathway to target for therapeutic interventions. © 2009 Sarma et al; licensee BioMed Central Ltd.

Continuity and Change in the European Union’s Approach to Enlargement::Turkey and Central and Eastern Europe compared

Existing studies of European Union (EU) enlargement provide few answers to questions concerning continuity and change in the dynamics of the process. This article identifies a number of conditioning factors that have shaped the EU’s approach to eastern enlargement and traces elements of continuity and change in the EU’s handling of Turkey’s membership aspirations. The article focuses on three established factors – member state preferences, supranational activism and EU capacity – and two less prominent factors – public opinion and narrative frame

Abell 41: shaping of a planetary nebula by a binary central star

ABSTRACT We present the first detailed spatiokinematical analysis and modelling of the planetary nebula Abell 41, which is known to contain the well-studied close-binary system MT Ser. This object represents an important test case in the study of the evolution of planetary nebulae with binary central stars as current evolutionary theories predict that the binary plane should be aligned perpendicular to the symmetry axis of the nebula. Deep narrow-band imaging in the light of [NII]6584Å, [OIII]5007 Å and [SII]6717+6731Å, obtained using ACAM on the William Herschel Telescope, has been used to investigate the ionization structure of Abell 41. Long-slit observations of the Ha and [NII]6584Å emission were obtained using the Manchester Echelle Spectrometer on the 2.1-m San Pedro Mártir Telescope. These spectra, combined with the narrow-band imagery, were used to develop a spatiokinematical model of [NII]6584Å emission from Abell 41. The best-fitting model reveals Abell 41 to have a waisted, bipolar structure with an expansion velocity of ~40 km s-1 at the waist. The symmetry axis of the model nebula is within 5° of perpendicular to the orbital plane of the central binary system. This provides strong evidence that the close-binary system, MT Ser, has directly affected the shaping of its nebula, Abell 41. Although the theoretical link between bipolar planetary nebulae and binary central stars is long established, this nebula is only the second to have this link, between nebular symmetry axis and binary plane, proved observationally.