IL-10 control of dendritic cells in the skin

Interleukin-10 (IL-10) is a potent immunomodulatory cytokine, whose cellular targets have not yet been precisely identified. Mice bearing a dendritic cell (DC)-specific defect in the IL-10 receptor mice exhibit exaggerated T-cell reactivation in the skin, highlighting a key function of DCs in the maintenance of local immune homeostasis

Investigating the effect of soluble hydrogen on plasticity in low-symmetry alpha- uranium

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Dendritic cell-specific deletion of β-catenin results in fewer regulatory T-cells without exacerbating autoimmune collagen-induced arthritis

Dendritic cells (DCs) are professional antigen presenting cells that have the dual ability to stimulate immunity and maintain tolerance. However, the signalling pathways mediating tolerogenic DC function in vivo remain largely unknown. The β-catenin pathway has been suggested to promote a regulatory DC phenotype. The aim of this study was to unravel the role of β-catenin signalling to control DC function in the autoimmune collagen-induced arthritis model (CIA). Deletion of β-catenin specifically in DCs was achieved by crossing conditional knockout mice with a CD11c-Cre transgen

Whooper Swan Cygnus cygnus January population censuses for Northwest Mainland Europe, 1995-2015

Internationally coordinated censuses of Whooper Swans Cygnus cygnus across continental northwest Europe were undertaken in mid-winter 1995, 2000, 2005, 2010 and 2015. The estimate of 138,500 birds in 2015, the highest to date, represented a more than doubling of the population size (at an annual increase of 4.1%) since the first census total of 59,000 swans in 1995. The largest increase was in Denmark, where numbers almost trebled from 21,740 in 1995 to 62,620 in 2015. More than 97% of all swans were counted in just six countries. The percentage of total numbers increased significantly between 1995 and 2015 in Denmark (from 36.5% to 45.2%) and Germany (26.0% to 34.7%), but declined significantly in Sweden (14.2% to 8.4%), Norway (13.1% to 3.6%), Poland (6.2% to 4.0%) and the Netherlands (2.4% to 1.7%). The counts show an increasing discrepancy between national trends in abundance for Whooper Swans in Sweden and especially in Denmark in comparison with results obtained only from mid-winter International Waterbird Count (IWC) site coverage. This demonstrates the increasing tendency for Whooper Swans to winter in areas away from traditionally counted IWC sites and confirms the continued need for a regular cycle of coordinated dedicated swan counts to anchor population trends generated from other data sources.Peer reviewe

Tnfaip3 expression in pulmonary conventional type 1 Langerin-expressing dendritic cells regulates T helper 2-mediated airway inflammation in mice

Background: Conventional type 1 dendritic cells (cDC1s) control anti-viral and anti-tumor immunity by inducing antigen-specific cytotoxic CD8+ T-cell responses. Controversy exists whether cDC1s also control CD4+ T helper 2 (Th2) cell responses, since suppressive and activating roles have been reported. DC activation status, controlled by the transcription factor NF-κB, might determine the precise outcome of Th-cell differentiation upon encounter with cDC1s. To investigate the role of activated cDC1s in Th2-driven immune responses, pulmonary cDC1s were activated by targeted deletion of A20/Tnfaip3, a negative regulator of NF-κB signaling. Methods: To target pulmonary cDC1s, Cd207 (Langerin)-mediated excision of A20/Tnfaip3 was used, generating Tnfaip3fl/flxCd207+/cre (Tnfaip3Lg-KO) mice. Mice were exposed to house dust mite (HDM) to provoke Th2-mediated immune responses. Results: Mice harboring Tnfaip3-deficient cDC1s did not develop Th2-driven eosinophilic airway inflammation upon HDM exposure, but rather showed elevated numbers of IFNγ-expressing CD8+ T cells. In addition, Tnfaip3Lg-KO mice harbored increased numbers of IL-12–expressing cDC1s and elevated PD-L1 expression in all pulmonary DC subsets. Blocking either IL-12 or IFNγ in Tnfaip3Lg-KO mice restored Th2 responses, whereas administration of recombinant IFNγ during HDM sensitization in C57Bl/6 mice blocked Th2 development. Conclusions: These findings indicate that the activation status of cDC1s, shown by their specific expression of co-inhibitory molecules and cytokines, critically contributes to the development of Th2 cell–mediated disorders, most likely by influencing IFNγ production in CD8+ T cells

Effects of intervention with sulindac and inulin/VSL#3 on mucosal and luminal factors in the pouch of patients with familial adenomatous polyposis

Contains fulltext : 97862.pdf (publisher's version ) (Open Access)BACKGROUND/AIM: In order to define future chemoprevention strategies for adenomas or carcinomas in the pouch of patients with familial adenomatous polyposis (FAP), a 4-weeks intervention with (1) sulindac, (2) inulin/VSL#3, and (3) sulindac/inulin/VSL#3 was performed on 17 patients with FAP in a single center intervention study. Primary endpoints were the risk parameters cell proliferation and glutathione S-transferase (GST) detoxification capacity in the pouch mucosa; secondary endpoints were the short chain fatty acid (SCFA) contents, pH, and cytotoxicity of fecal water. METHODS: Before the start and at the end of each 4-week intervention period, six biopsies of the pouch were taken and feces was collected during 24 h. Cell proliferation and GST enzyme activity was assessed in the biopsies and pH, SCFA contents, and cytotoxicity were assessed in the fecal water fraction. The three interventions (sulindac, inulin/VSL#3, sulindac/inulin/VSL#3) were compared with the Mann-Whitney U test. RESULTS: Cell proliferation was lower after sulindac or VSL#3/inulin, the combination treatment with sulindac/inulin/VSL#3 showed the opposite. GST enzyme activity was increased after sulindac or VSL#3/inulin, the combination treatment showed the opposite effect. However, no significance was reached in all these measures. Cytotoxicity, pH, and SCFA content of fecal water showed no differences at all among the three treatment groups. CONCLUSION: Our study revealed non-significant decreased cell proliferation and increased detoxification capacity after treatment with sulindac or VSL#3/inulin; however, combining both regimens did not show an additional effect

On the evolution and modelling of lattice strains during the cyclic loading of TWIP steel

The evolution of lattice strains in fully annealed Fe–24Mn–3Al–2Si–1Ni–0.06C twinning-induced plasticity (TWIP) steel is investigated via in situ neutron diffraction during cyclic (tension–compression) loading between strain limits of ±1%. The pronounced Bauschinger effect observed upon load reversal is accounted for by a combination of the intergranular residual stresses and the intragranular sources of back stress, such as dislocation pile-ups at the intersection of stacking faults. The recently modified elasto-plastic self-consistent (EPSC) model which empirically accounts for both intergranular and intragranular back stresses has been successfully used to simulate the macroscopic stress–strain response and the evolution of the lattice strains. The EPSC model captures the experimentally observed tension–compression asymmetry as it accounts for the directionality of twinning as well as Schmid factor considerations. For the strain limits used in this study, the EPSC model also predicts that the lower flow stress on reverse shear loading reported in earlier Bauschinger-type experiments on TWIP steel is a geometrical or loading path effect