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

Expression of Genes Encoding Multi-Transmembrane Proteins in Specific Primate Taste Cell Populations

BACKGROUND: Using fungiform (FG) and circumvallate (CV) taste buds isolated by laser capture microdissection and analyzed using gene arrays, we previously constructed a comprehensive database of gene expression in primates, which revealed over 2,300 taste bud-associated genes. Bioinformatics analyses identified hundreds of genes predicted to encode multi-transmembrane domain proteins with no previous association with taste function. A first step in elucidating the roles these gene products play in gustation is to identify the specific taste cell types in which they are expressed. METHODOLOGY/PRINCIPAL FINDINGS: Using double label in situ hybridization analyses, we identified seven new genes expressed in specific taste cell types, including sweet, bitter, and umami cells (TRPM5-positive), sour cells (PKD2L1-positive), as well as other taste cell populations. Transmembrane protein 44 (TMEM44), a protein with seven predicted transmembrane domains with no homology to GPCRs, is expressed in a TRPM5-negative and PKD2L1-negative population that is enriched in the bottom portion of taste buds and may represent developmentally immature taste cells. Calcium homeostasis modulator 1 (CALHM1), a component of a novel calcium channel, along with family members CALHM2 and CALHM3; multiple C2 domains; transmembrane 1 (MCTP1), a calcium-binding transmembrane protein; and anoctamin 7 (ANO7), a member of the recently identified calcium-gated chloride channel family, are all expressed in TRPM5 cells. These proteins may modulate and effect calcium signalling stemming from sweet, bitter, and umami receptor activation. Synaptic vesicle glycoprotein 2B (SV2B), a regulator of synaptic vesicle exocytosis, is expressed in PKD2L1 cells, suggesting that this taste cell population transmits tastant information to gustatory afferent nerve fibers via exocytic neurotransmitter release. CONCLUSIONS/SIGNIFICANCE: Identification of genes encoding multi-transmembrane domain proteins expressed in primate taste buds provides new insights into the processes of taste cell development, signal transduction, and information coding. Discrete taste cell populations exhibit highly specific gene expression patterns, supporting a model whereby each mature taste receptor cell is responsible for sensing, transmitting, and coding a specific taste quality

Genome-Wide Analysis of Gene Expression in Primate Taste Buds Reveals Links to Diverse Processes

Efforts to unravel the mechanisms underlying taste sensation (gustation) have largely focused on rodents. Here we present the first comprehensive characterization of gene expression in primate taste buds. Our findings reveal unique new insights into the biology of taste buds. We generated a taste bud gene expression database using laser capture microdissection (LCM) procured fungiform (FG) and circumvallate (CV) taste buds from primates. We also used LCM to collect the top and bottom portions of CV taste buds. Affymetrix genome wide arrays were used to analyze gene expression in all samples. Known taste receptors are preferentially expressed in the top portion of taste buds. Genes associated with the cell cycle and stem cells are preferentially expressed in the bottom portion of taste buds, suggesting that precursor cells are located there. Several chemokines including CXCL14 and CXCL8 are among the highest expressed genes in taste buds, indicating that immune system related processes are active in taste buds. Several genes expressed specifically in endocrine glands including growth hormone releasing hormone and its receptor are also strongly expressed in taste buds, suggesting a link between metabolism and taste. Cell type-specific expression of transcription factors and signaling molecules involved in cell fate, including KIT, reveals the taste bud as an active site of cell regeneration, differentiation, and development. IKBKAP, a gene mutated in familial dysautonomia, a disease that results in loss of taste buds, is expressed in taste cells that communicate with afferent nerve fibers via synaptic transmission. This database highlights the power of LCM coupled with transcriptional profiling to dissect the molecular composition of normal tissues, represents the most comprehensive molecular analysis of primate taste buds to date, and provides a foundation for further studies in diverse aspects of taste biology

Identification of a novel secreted molecule expressed by Th17 cells: potential association with inflammatory diseases. (59.3)

Abstract CD4 T cells (Th cells) play an important role in adaptive immune responses. These processes are controlled in part by a pattern of soluble molecules (cytokines) secreted by different types of Th cells. Here we describe a novel secreted molecule which we have called barrier tissue and activated T cell-associated molecule (BATAM). Using a comprehensive database of human gene expression that comprises more than 115 tissues or organs of the body, we identified a secreted protein that is produced by activated CD4 T cells as well as skin and various mucosal tissues. BATAM encodes a ~60 KD protein that contains a thrombospondin type 1 repeat (TSR) and the adhesion associated domain AMOP, which are known to mediate cell adhesion and are also present in various proteins involved in inflammation. We confirmed the BATAM expression pattern by qPCR in mouse tissues. The production of BATAM by activated spleen CD4 T cells is significant but not strong. We therefore hypothesized that BATAM may be preferentially produced by a polarized subset of Th cells. To investigate this possibility, we polarized CD4 T cells into Th1, Th2, Treg and Th17 in vitro. The results indicate that BATAM expression is highly associated with Th17 cells. We have also confirmed that it is a secreted protein. Using recombinant BATAM, we are currently probing its biological activity. We conclude that BATAM is a novel pro-inflammatory molecule that may be associated with diseases mediated by Th17 cells.</jats:p

Nogo B Receptor is expressed in a subset of T cells; is AmNogoB a cytokine? (57.21)

Abstract The Reticulon/Nogo is a large family of proteins, which share the C-terminal region of approximately 200 aa, called the Reticulon homology domain (RHD). Many of these molecules have been identified in the Central Nervous System and that is where most studies have focused so far. The best characterized gene of the Reticulon family is RTN4. It is composed of three isoforms: RTN4/Nogo A, RTN4/Nogo B and RTN/Nogo C. Nogo B plays an essential role in vascular remodeling and appears to be important in angiogenesis and metabolic processes. Interestingly, the amino terminal region of Nogo B (amNogo B), can be a soluble peptide that promotes vascular adhesion and migration of endothelial cells by binding the recently reported Nogo B receptor (NgBR). Using a comprehensive database of gene expression in the human body, we made the unexpected observation that the cells exhibiting the strongest expression of NgBR include activated CD4+ and CD8+ T cells. We have confirmed that NgBR is expressed in a subpopulation of activated T cells expressing the activation marker CD69 in mouse, indicating the existence of a new subpopulation of activated T cells that are NgBR+CD69+. Since amNogoB is present in plasma, it should be able to bind this new subpopulation of activated T cells via NgBR and therefore it may play a role in modulating T cell activation. We are currently studying the functional consequences of the amNogoB:NgBR interaction in activated T cells.</jats:p

The top skin-associated genes: a comparative analysis of human and mouse skin transcriptomes

Abstract The mouse represents a key model system for the study of the physiology and biochemistry of skin. Comparison of skin between mouse and human is critical for interpretation and application of data from mouse experiments to human disease. Here, we review the current knowledge on structure and immunology of mouse and human skin. Moreover, we present a systematic comparison of human and mouse skin transcriptomes. To this end, we have recently used a genome-wide database of human gene expression to identify genes highly expressed in skin, with no, or limited expression elsewhere – human skin-associated genes (hSAGs). Analysis of our set of hSAGs allowed us to generate a comprehensive molecular characterization of healthy human skin. Here, we used a similar database to generate a list of mouse skin-associated genes (mSAGs). A comparative analysis between the top human (n=666) and mouse (n=873) skin-associated genes (SAGs) revealed a total of only 30.2% identity between the two lists. The majority of shared genes encode proteins that participate in structural and barrier functions. Analysis of the top functional annotation terms revealed an overlap for morphogenesis, cell adhesion, structure, and signal transduction. The results of this analysis, discussed in the context of published data, illustrate the diversity between the molecular make up of skin of both species and grants a probable explanation, why results generated in murine in vivo models often fail to translate into the human.</jats:p