Correction to: EGFR/Ras-induced CCL20 production modulates the tumour microenvironment

The article ‘EGFR/Ras-induced CCL20 production modulates the tumour microenvironment’, written by Andreas Hippe, Stephan Alexander Braun, Péter Oláh, Peter Arne Gerber, Anne Schorr, Stephan Seeliger, Stephanie Holtz, Katharina Jannasch, Andor Pivarcsi, Bettina Buhren, Holger Schrumpf, Andreas Kislat, Erich Bünemann, Martin Steinhoff, Jens Fischer, Sérgio A. Lira, Petra Boukamp, Peter Hevezi, Nikolas Hendrik Stoecklein, Thomas Hoffmann, Frauke Alves, Jonathan Sleeman, Thomas Bauer, Jörg Klufa, Nicole Amberg, Maria Sibilia, Albert Zlotnik, Anja Müller- Homey and Bernhard Homey, was originally published electronically on the publisher’s internet portal on 30 June 2020 without open access. With the author(s)’ decision to opt for Open Choice the copyright of the article changed on 16 September 2021 to © The Author(s) 2021 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0/. Open Access funding enabled and organized by Projekt DEAL

All-sky Medium Energy Gamma-ray Observatory: Exploring the Extreme Multimessenger Universe

The All-sky Medium Energy Gamma-ray Observatory (AMEGO) is a probe class mission concept that will provide essential contributions to multimessenger astrophysics in the late 2020s and beyond. AMEGO combines high sensitivity in the 200 keV to 10 GeV energy range with a wide field of view, good spectral resolution, and polarization sensitivity. Therefore, AMEGO is key in the study of multimessenger astrophysical objects that have unique signatures in the gamma-ray regime, such as neutron star mergers, supernovae, and flaring active galactic nuclei. The order-of-magnitude improvement compared to previous MeV missions also enables discoveries of a wide range of phenomena whose energy output peaks in the relatively unexplored medium-energy gamma-ray band

Anti-inflammatory consequences of bile acid accumulation in virus-infected bile duct ligated mice.

Cholestatic patients exhibiting high bile acid serum levels were reported to be more susceptible to bacterial and viral infections. Animal studies in bile duct ligated (BDL) mice suggest that cholestasis leads to an aggravation of hepatic bacterial infections. We have investigated the impact of cholestasis on mouse cytomegalovirus (MCMV)-induced immune responses and viral replication. While MCMV did not aggravate BDL-induced liver damage, BDL markedly reduced MCMV-triggered chemokine expression and immune cell recruitment to the liver. MCMV-infected BDL mice showed diminished trafficking of Ly6C+/F4/80+ myeloid cells and NK1.1+ NK cells to the liver compared to MCMV infected control mice. Moreover, virus-driven expression of CCL7, CCL12, CXCL9 and CXCL10 was clearly impaired in BDL- compared to sham-operated mice. Furthermore, production of the anti-inflammatory cytokine IL-10 was massively augmented in infected BDL mice. In contrast, intra- and extrahepatic virus replication was unaltered in BDL-MCMV mice when compared to sham-MCMV mice. Cholestasis in the BDL model severely impaired pathogen-induced chemokine expression in the liver affecting CCR2- and CXCR3-dependent cell trafficking. Cholestasis resulted in reduced recruitment of inflammatory monocytes and NK cells to the liver

Structure and Dynamics of Human Chemokine CCL16—Implications for Biological Activity

Human C-C motif ligand 16 (CCL16) is a chemokine that is distinguished by a large cleavable C-terminal extension of unknown significance. Conflicting data have been reported concerning its tissue distribution and modulation of expression, rendering the biological function of CCL16 enigmatic. Here, we report an integrated approach to the characterisation of this chemokine, including a re-assessment of its expression characteristics as well as a biophysical investigation with respect to its structure and dynamics. Our data indicate that CCL16 is chiefly synthesised by hepatocytes, without an appreciable response to mediators of inflammation, and circulates in the blood as a full-length protein. While the crystal structure of CCL16 confirms the presence of a canonical chemokine domain, molecular dynamics simulations support the view that the C-terminal extension impairs the accessibility of the glycosaminoglycan binding sites and may thus serve as an intrinsic modulator of biological activity

BDL modifies plasma chemokine and cytokine levels.

<p>Blood of sham- or BDL-operated animals that were either mock or MCMV-luc (2x10⁵ PFU/ml) infected was collected 24 and 72 hpi. Plasma protein levels of (A) CCL7, (B) CXCL10 or (C) IL-10 were measured using a magnetic screening assay. Depicted are the mean values ± SEM from the indicated mouse groups (24 hpi: sham n = 8; BDL n = 10; sham-MCMV n = 10; BDL-MCMV n = 10; 72 hpi: sham n = 5; BDL n = 4; sham-MCMV n = 9; BDL-MCMV n = 9). Statistical significance was calculated with Mann-Whitney-U-tests (***p< 0.001, **p< 0.01, *p< 0.05, ns: not significant).</p

BDL alters the immune cell profile of MCMVinfected livers.

<p>Sham- or BDL-operated mice were either mock treated or infected with MCMV-luc (2x10⁵ PFU/ml) and 72 hpi organs were harvested. Total RNA of liver tissue was prepared and cell marker mRNA expression was analyzed by qPCR using specific TaqMan primers and probes. Relative gene expression was calculated by the ΔΔCt method using RPII or SDHA as housekeeping gene. Depicted are the mean values ± SEM of (A) PLZF, (B) CD11b, (C) Ly6C, (D) F4/80, (E) NK1.1 and (F) CD335 from the indicated groups of mice (sham n = 5; BDL n = 4; sham MCMV n = 9; BDL MCMV n = 9). Statistical significance was calculated with Mann-Whitney-U-tests (***p< 0.001, **p< 0.01, *p< 0.05, ns: not significant).</p

BDL is not associated with diminished MCMV replication.

<p>Sham or BDL operated mice were infected with MCMV-luc (2x10⁵ PFU/ml) and 72 hpi organs were harvested. Total RNA of liver or spleen tissue was prepared and MCMV <i>ie3</i> mRNA expression was analyzed by qPCR using specific primers or TaqMan primers and probes. Relative gene expression was calculated by the ΔΔCt method using RPII or SDHA as housekeeping gene. Depicted are the mean values ± SEM of (A) liver tissue and (B) spleen tissue 72 hpi from the indicated groups of mice (sham-MCMV n = 9; BDL-MCMV n = 9). Statistical significance was calculated with Mann-Whitney-U-tests. Organ homogenates of (C) livers or (D) spleens were generated 72 hpi and virus-tissue suspensions were titrated on murine fibroblasts. 24 h post titration luciferase activity was measured and virus titers were calculated using a standard curve. Each square represents one sample, the black line illustrates the median of each group and the dotted line displays the detection limit. Statistical significance was calculated with Mann-Whitney-U-tests (ns: not significant).</p

BDL leads to increased bile acid concentrations in blood plasma.

<p>BDL leads to increased bile acid concentrations in blood plasma.</p