Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

Some studies have shown that cytotoxic T lymphocytes are able to recognize tumor ceNs but tumorinfiltrating lymphocytes (TIL) seem to have functional defects. The group of Pierre van der Bruggen has shown that the functional impairment observed in tumor-infiltrating lymphocytes could be corrected by treatments with galectin competitor ligands. This suggests that galectins that are abundant in tumors could be responsible for these defects. In contrast with blood CD8 T cells, TIL that were treated with LacNAC, a galectin competitor ligand, and stimulated ex vivo secreted more IFN-y than untreated TIL. We have tried to better understand the defect of TIL by examining whether IFN-y production or secretion is affected. We have also investigated cytoskeleton remodeling which contributes to the secretory machinery. We performed intracellular staining of IFN-y after ex vivo stimulation. No difference was observed between LacNAc-treated and non-treated TIL samples. We also quantified the cytokine mRNA using qPCR. Despite important variations between samples, LacNAc treatment did not seem to influence the level of IFN-y mRNA in TIL. These results indicate that IFN-y is produced after TIL ex vivo stimulation and suggest that the difference observed at the secretion level is neither due to a lack of activation of the TIL nor to a defect in the cytokine production. We temporarily concluded that untreated TIL are poorly able to secrete IFN-y. We have examined TIL by confocal microscopy with a focus on microtubule network and actin cytoskeleton, which have been associated with secretion in lymphocytes. We studied the polarization of the Microtubule Organizing Center (MTOC) of the TIL towards the target. We observed a defect of MTOC docking at the synapse between untreated TIL and antigen presenting cells. MTOC docking was improved in LacNAc-treated TIL. In another unrelated project, we have produced recombinant galectin-1 with the objective to better understand the mechanisms underlying the role of galectins in TIL defects. This protein wiIl be useful in the laboratory to assess, in the future, the ability of galectin-1 and -3 to induce CD8 T cells dysfunction in vitro Plusieurs études ont démontré que les lymphocytes T cytotoxiques, bien qu’équipés pour éliminer les cellules cancéreuses, ne fonctionnent pas correctement lorsqu’ils sont dans les tumeurs. L’équipe de Pierre van der Bruggen a récemment montré que des lymphocytes T CD8 infiltrant les tumeurs (TIL) présentaient des défauts fonctionnels probablement imputables à une protéine abondante dans les tumeurs, la galectine-3. Il a notamment été observé, ex-vivo, que les lymphocytes T CD8 infiltrant les tumeurs, contrairement aux CD8 sanguins montrent un défaut de sécrétion d’interféron-gamma après restimulation. Ce défaut peut être levé par des ligands compétiteurs des galectines, comme le LacNAc. Notre projet s’insère dans les efforts de l’équipe pour mieux comprendre les mécanismes de ces déficiences fonctionnelles et a pour but de déterminer si le défaut se situe au niveau de la production de la protéine ou de sa sécrétion et si des perturbations dans le remodelage du cytosquelette sont impliquées. Nous avons étudié, dans les TIL CD8, la production de l’ARN messager de l’interféron-gamma par PCR quantitative. Nos résultats semblent indiquer que le niveau d’ARN messager est le même dans les TIL qu’ils aient ou non été traités au LacNAc avant d’être stimulés. Nous avons également analysé la production de la protéine par marquage intracellulaire et analyse en cytométrie en flux. La proportion de cellules positives pour l’IFN-y était similaire dans les échantillons traités ou non au LacNAc. Nos résultats suggèrent donc que les TIL soient capables de s’activer et de produire la cytokine mais qu’ils soient incapables de la sécréter correctement. Des défauts de remodelage du cytosquelette de ces TIL pourraient expliquer le déficit de sécrétion d’interféron-gamma observé. En effet, il est connu que l’organisation des microfilaments de tubuline et d’actine participe à l’exocytose des cytokines. Pour étudier cette hypothèse, nous avons développé une technique permettant d’observer, en microscopie confocale, les remodelages du cytosquelette induits par la rencontre entre un lymphocyte T et sa cible. Nous nous sommes intéressés en particulier au centre organisateur des microtubules (MTOC) et à sa polarisation vers la cible du lymphocyte T, à la synapse immunologique. Nous avons observé que, dans les TIL CD8, restimulés ex-vivo, le MTOC ne s’ancre pas toujours à la membrane au point de contact avec la cible, ce qui pourrait expliquer le défaut de sécrétion observé. Un traitement des TIL au LacNAc remédie largement à ce défaut. Certaines expériences, dans la littérature, suggèrent que la galectine-3 pourrait ne pas être seule galectine responsable du dysfonctionnement des lymphocytes T infiltrant les tumeurs. Nous avons donc produit de la galectine-1 recombinante dans le but d’étudier si elle peut induire, in-vitro, ces dysfonctionnements des lymphocytes, seule, ou en combinaison avec la galectine-3.

T-Lymphocytes, Cytotoxic --- Galectins --- Neoplasms --- Lymphocytes, Tumor-Infiltrating

Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

Glucocorticoids --- Growth hormone --- Sympathetic innervation --- Galectins --- Thymus --- Norepinephrine --- Ephrins --- Diabetes --- Infectious diseases --- Cytokines

Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

In the past decade, there has been an explosion of progress in understanding the roles of carbohydrates in biological systems. This explosive progress was made with the efforts in determining the roles of carbohydrates in immunology, neurobiology and many other disciplines, examining each unique system and employing new technology. This volume represents the second of three in the Methods in Enzymology series, including Glycobiology (vol. 415) and Glycomics (vol. 416), dedicated to disseminating information on methods in determining the biological roles of carbohydrates. These books are

Analysis. --- Carbohydrates. --- Chemistry. --- Etiology. --- Galectins. --- Glycolipids. --- Glycomics. --- Methods. --- Muscular Dystrophies. --- Physiology. --- Proteomics. --- Chemicals and Drugs --- Lipids --- Glycoconjugates --- Glycolipids --- Carbohydrates --- Glycobiology --- Genomics --- Molecular biology

Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

Galectins are a family of soluble beta-galactoside-binding proteins with diverse glycan-dependent and glycan-independent functions outside and inside the cell. There are sixteen recognized mammalian galectin genes, and their expression profiles are very different between cell types, tissues, and species. This Special Issue covers recent progress in the field of the cell biology of galectins, relevant concepts of galectin regulatory mechanisms, and biomedical aspects of these unique multifunctional proteins.

galectin-7 --- p53 --- MMP-9 --- cancer --- gain-of-function --- vasculature --- gene expression --- tube formation --- sprouting --- VEGF --- integrins --- galectin --- extracellular matrix --- microenvironment --- Yersinia enterocolitica --- YopP --- Galectin-1 --- nitric oxide --- macrophages --- epithelial tissues --- apoptosis --- targeting --- inhibitors --- β-hairpin --- β-sandwich --- blood group B --- lectin --- sugar code --- LGALS16 --- placenta --- brain tissues --- cell differentiation --- transcription factor --- miRNA --- galectin-3 --- cardiac fibrosis --- heart failure --- atrial fibrillation --- chronic inflammation --- MMPs --- microRNAs --- lncRNAs --- pectin --- structure and function --- bioactive polysaccharides --- galectin-3 inhibition --- galacto-oligosaccharides --- galectins --- intestinal epithelial cells --- β-3′galactosyllactose --- immunomodulation --- mucosal immunity --- O-GlcNAc --- unconventional secretion --- extraembryonic endoderm --- n/a --- β-3'galactosyllactose

Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

Marine creatures are rich sources of glycoconjugate-containing glycans and have diversified structures. The advance of genomics has provided a valuable clue for their production and developments. This information will encourage breeding and engineering functional polysaccharides with slime ingredients in algae. These glycans will have the potential for applications to antioxidant, anticancer, and antimicrobial drugs in addition to health supplements and cosmetics. The combination of both biochemical and transcriptome approaches of marine creatures will lead to the opportunity to discover new activities of proteins such as glycan-relating enzymes and lectins. These proteins will also be used for experimental and medical purposes, such as diagnostics and trial studies. The topic of marine glycomics is also focusing on understanding the physiological properties of marine creatures, such as body defense against pathogens and cancers. In the competitions for natural selection, living creatures have evolved both their glycans and their recognition. They have primitive systems of immunity, and few of their mechanisms are closely related to glycans. If we are able to describe the accumulation of data of glycans of creatures living in the seashore and the oceans, we may be able to anticipate a time when we can talk about the ecosystem with glycans. That knowledge will be useful for the development of drugs that cure our diseases and for an understanding of living systems in addition to the preservation of living environments.

Research & information: general --- Biology, life sciences --- Acropora tenuis --- coral --- chemoattraction --- lectin --- white-spotted charr lectin --- oncolytic vaccinia virus --- interferon --- antiviral response --- Chlorella vulgaris --- Dunaliella salina --- Arthrospira platensis --- growth rate --- accumulation of carbohydrates --- biohydrogen --- antibacterial activity --- anticancer activity --- antifungal activity --- Aplysia kurodai --- apoptosis --- Ehrlich ascites carcinoma --- sulfated fucose-rich polysaccharides --- sulfated fucan --- fucosylated chondroitin sulfate --- fucoidan --- oral administration --- anticoagulant activity --- fucosylated glycosaminoglycan --- anticoagulant --- platelet aggregation --- contact activation --- hypotension --- pulmonary embolism --- sulfated polysaccharides --- marine hydrobionts --- antiparasitic activity --- protozoa --- malaria --- leishmaniasis --- trypanosomiasis --- schistosomiasis --- cryptosporidiosis --- trichomoniasis --- bivalve mollusk --- C1q domain-containing --- lectin-like --- pattern recognition receptor --- polysaccharides --- interstitial compartment --- marine worms --- sipunculids --- bioactive properties --- peptides --- rotifera --- pattern recognition receptors --- microbe-associated molecular patterns --- innate immunity --- C-type lectins --- C1q domain-containing proteins --- galectins --- bacterial exopolysaccharides --- bioflocculanting activity --- microalgae growth-promoting bacterium --- harmful algal bloom-forming dinoflagellate --- Alexandrium catenella --- Mameliella alba --- n/a