Low-dose 2-Deoxy Glucose Stabilises Tolerogenic Dendritic Cells and Generates Potent in vivo Immunosuppressive Effects

Open Access via Springer Compact Agreement University of Aberdeen Development Trust Grant number RG14251, RG12663 Acknowledgements: We thank the University of Aberdeen Iain Fraser Flow Cytometry core facility, and the University of Aberdeen Histology and Microscopy core facility for processing of histology slides. The authors thank University of Aberdeen Medical Research Facility for technical assistance with in vivo experiments. We thank Dr. Tian Yu, Dr. Yi-Hsia Liu, Mrs Rosemary Fordyce, and Mrs Elizabeth Muckersie for technical assistance with in vivo and in vitro experiments. Funding: This work was supported by funds from the University of Aberdeen Development Trust Grants RG14251 and RG12663. Maria Christof was the recipient of a University of Aberdeen PhD Studentship. Samantha Le Sommer was funded by a Wellcome Trust ISSF Postdoctoral Fellowship.Peer reviewedPublisher PD

Colitis in a transgenic mouse model of autoimmune uveitis may be induced by neoantigen presentation in the bowel

Undifferentiated uveitis (intraocular inflammation, IOI) is an idiopathic sight-threatening, presumed autoimmune disease, accountable for ~ 10% of all blindness in the developed world. We have investigated the association of uveitis with inflammatory bowel disease (IBD) using a mouse model of spontaneous experimental autoimmune uveoretinitis (EAU). Mice expressing the transgene (Tg) hen egg lysozyme (HEL) in the retina crossed with 3A9 mice expressing a transgenic HEL-specific TCR spontaneously develop uveoretinitis at post-partum day (P)20/21. Double transgenic (dTg TCR/HEL) mice also spontaneously develop clinical signs of colitis at ~ P30 with diarrhoea, bowel shortening, oedema and lamina propria (LP) inflammatory cell infiltration. Single (s)Tg TCR (3A9) mice also show increased histological LP cell infiltration but no bowel shortening and diarrhoea. dTg TCR/HEL mice are profoundly lymphopenic at weaning. In addition, dTg TCR/HEL mice contain myeloid cells which express MHC Class II-HEL peptide complexes (MHCII-HEL), not only in the inflamed retina but also in the colon and have the potential for antigen presentation. In this model the lymphopenia and reduction in the absolute Treg numbers in dTg TCR/HEL mice is sufficient to initiate eye disease. We suggest that cell-associated antigen released from the inflamed eye can activate colonic HEL-specific T cells which, in a microbial micro-environment, not only cause colitis but feedback to amplify IOI

Cobalt--zinc molybdates as new blue pigments involving Co²⁺ in distorted trigonal bipyramids and octahedra

Zn1-xCoxMoO4 (x Pt space group. X-ray diffraction and Rietveld analyses reveal the occurrence of three highly distorted sites with equal occupancies corresponding to one trigonal bipyramidal CoO5 group and two octahedral CoO6 groups occupied by either Zn2+ or Co2+. Mo6+ ions are located in distorted tetrahedral sites. Electron paramagnetic resonance analysis allows characterization of the two kinds of environments with orthorhombic distortion related to two signals with different g values. The UV-vis spectra exhibit intense Co2+ d-d transitions associated with CoO5 and CoO6 chromophores between 1.9 and 2.6 eV in the visible domain and O-Mo charge transfer at the frontier between the UV and visible ranges. A blue-transmitted window can then be displayed. The formation of covalent MoO4 entities and polarizable Zn2+ cations creating highly distorted noncentrosymmetric sites partially occupied by Co2+ allows stabilization of the first blue pigment without Co2+ in the tetrahedral environment. Moreover, only 5-10% cobalt is necessary to get a strong blue hue because of the highly distorted sites leading to very important oscillator strengths