Search

Your search keyword '"Georgopoulos K"' showing total 201 results
Start Over Author "Georgopoulos K"
201 results on '"Georgopoulos K"'

1. XR-RF Imaging Enabled by Software-Defined Metasurfaces and Machine Learning: Foundational Vision, Technologies and Challenges

Author

Liaskos, C., Tsioliaridou, A., Georgopoulos, K., Morianos, G., Ioannidis, S., Salem, I., Manessis, D., Tyrovolas, S. Schmid D., Tegos, S. A., Mekikis, P. -V., Diamantoulakis, P. D., Pitilakis, A., Kantartzis, N., Tasolamprou, G. K. Karagiannidis A., Tsilipakos, O., Kafesaki, M., Akyildiz, I. F., Pitsillides, A., Pateraki, M., Vakalellis, M., and Spais, I.

Subjects
Electrical Engineering and Systems Science - Signal Processing, Computer Science - Emerging Technologies, Electrical Engineering and Systems Science - Image and Video Processing
Abstract

We present a new approach to Extended Reality (XR), denoted as iCOPYWAVES, which seeks to offer naturally low-latency operation and cost-effectiveness, overcoming the critical scalability issues faced by existing solutions. iCOPYWAVES is enabled by emerging PWEs, a recently proposed technology in wireless communications. Empowered by intelligent (meta)surfaces, PWEs transform the wave propagation phenomenon into a software-defined process. We leverage PWEs to i) create, and then ii) selectively copy the scattered RF wavefront of an object from one location in space to another, where a machine learning module, accelerated by FPGAs, translates it to visual input for an XR headset using PWEdriven, RF imaging principles (XR-RF). This makes for an XR system whose operation is bounded in the physical layer and, hence, has the prospects for minimal end-to-end latency. Over large distances, RF-to-fiber/fiber-to-RF is employed to provide intermediate connectivity. The paper provides a tutorial on the iCOPYWAVES system architecture and workflow. A proof-of-concept implementation via simulations is provided, demonstrating the reconstruction of challenging objects in iCOPYWAVES produced computer graphics.

Published
2022
Full Text
View/download PDF

8. Treatment compliance and severe adverse events limit the use of tyrosine kinase inhibitors in refractory thyroid cancer

Author

Chrisoulidou A, Mandanas S, Margaritidou E, Mathiopoulou L, Boudina M, Georgopoulos K, and Pazaitou-Panayiotou K

Subjects
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282
Abstract

Alexandra Chrisoulidou, Stylianos Mandanas, Efterpi Margaritidou, Lemonia Mathiopoulou, Maria Boudina, Konstantinos Georgopoulos, Kalliopi Pazaitou-PanayiotouDepartment of Endocrinology, Theagenio Cancer Hospital, Thessaloniki, GreeceObjective: The aim of the present study was to assess patient compliance with tyrosine kinase inhibitor (TKI) treatment used for refractory and progressive thyroid cancer, in addition to the efficacy and serious adverse events associated with these agents.Methods: We retrospectively analyzed data from adult patients with metastatic differentiated or medullary thyroid cancer unresponsive to conventional treatment and treated with TKIs. Patients received treatment until disease progression or onset of serious adverse events, or until they expressed an intention to stop treatment.Results: Twenty-four patients received TKIs. The median duration of treatment was four (range: 1–19) cycles. The most frequent adverse events were fatigue, nausea, diarrhea, hypertension, and stomatitis, and the most severe were nasal bleeding, diarrhea, heart failure, rhabdomyolysis, renal failure, QT prolongation, neutropenia, and severe fatigue. Dose reduction was required in eight patients, while five decided to terminate TKI therapy because adverse events impaired their everyday activities. During therapy, two patients showed a partial response and three showed stable disease. The lungs were the metastatic sites favoring a response to treatment.Conclusion: Patient selection and meticulous pretreatment education are necessary in order to ensure adherence with TKI therapy. If adverse events appear, dose reduction or temporary treatment interruption may be offered because some adverse events resolve with continuation of treatment. In the event of serious adverse events, treatment discontinuation is necessary. Keywords: medullary thyroid carcinoma, differentiated thyroid cancer, TKIs, sorafenib, sunitinib, vandetanib

Published
2015

9. The T-Cell Receptor/T3 Complex

Author

Terhorst, C., Georgopoulos, K., Gold, P., Oettgen, H., Pettey, C., Ucker, D., van den Elsen, P., Feldmann, Marc, editor, and McMichael, Andrew, editor

Published
1986
Full Text
View/download PDF

10. Assembly of the T Cell Receptor/CD3 Complex

Author

Terhorst, C., Alarcon, B., Berkhout, B., Blumberg, R., Clevers, H., Georgopoulos, K., Hall, C., Ley, S., Sancho, J., Versteegen, J., Wileman, Th., Melchers, Fritz, editor, Albert, E. D., editor, von Boehmer, H., editor, Dierich, M. P., editor, Du Pasquier, L., editor, Eichmann, K., editor, Gemsa, D., editor, Götze, O., editor, Kalden, J. R., editor, Kaufmann, S. H. E., editor, Kirchner, H., editor, Resch, K., editor, Riethmüller, G., editor, Schimpl, A., editor, Sorg, C., editor, Steinmetz, M., editor, Wagner, H., editor, and Zachau, H. G., editor

Published
1989
Full Text
View/download PDF

12. Helios transcription factor expression depends on Gsx2 and Dlx1&2 function in developing striatal matrix neurons

Author

Martín-Ibáñez, R., Crespo, Empar, Esgleas, M., Urbán, Noelia, Wang, B., Waclaw, R., Georgopoulos, K., Martínez, Salvador, Campbell, K., Vicario-Abejón, Carlos, Alberch, J., Chan, S., Kastner, P., Rubenstein, John L., Canals, Josep María, Martín-Ibáñez, R., Crespo, Empar, Esgleas, M., Urbán, Noelia, Wang, B., Waclaw, R., Georgopoulos, K., Martínez, Salvador, Campbell, K., Vicario-Abejón, Carlos, Alberch, J., Chan, S., Kastner, P., Rubenstein, John L., and Canals, Josep María

Abstract

Development of the nervous system is finely regulated by consecutive expression of cell-specific transcription factors. Here we show that Helios, a member of the Ikaros transcription factor family, is expressed in ectodermal and neuroectodermal-derived tissues. During embryonic development, Helios is expressed by several brain structures including the lateral ganglionic eminence (LGE, the striatal anlage); the cingulated, insular and retrosplenial cortex; the hippocampus; and the accessory olfactory bulb. Moreover, Helios is also expressed by Purkinje neurons during postnatal cerebellar development. Within the LGE, Helios expression follows a dynamic spatio-temporal pattern starting at embryonic stages (E14.5), peaking at E18.5, and completely disappearing during postnatal development. Helios is expressed by a small population of nestin-positive neural progenitor cells located in the subventricular zone as well as by a larger population of immature neurons distributed throughout the mantle zone. In the later, Helios is preferentially expressed in the matrix compartment, where it colocalizes with Bcl11b and Foxp1, well-known markers of striatal projection neurons. In addition, we observed that Helios expression is not detected in Dlx1/2 and Gsx2 null mutants, while its expression is maintained in Ascl1 mutants. These findings allow us to introduce a new transcription factor in the cascade of events that take part of striatal development postulating the existence of at least 4 different neural progenitors in the LGE. An Ascl1-independent but Gsx2-& Dlx1/2-dependent precursor will express Helios defining a new lineage for a subset of matrix striatal neurons. © 2012, Mary Ann Liebert, Inc.

Published
2012

13. A novel approach for online sensor testing based on an encoded test stimulus

Author

Dumas, N., Xu, Z., Georgopoulos, K., Bunyan, R. J. T., Richardson, A., Dumas, N., Xu, Z., Georgopoulos, K., Bunyan, R. J. T., and Richardson, A.

Abstract

This paper presents a technique that enables online testing of sensors through the superposition of the test stimulus onto the measurand Perturbations due to the surrounding environment can very often introduce fluctuations in the test output that is a major concern for this type of sensor testing. This paper proposes a novel approach to tackle this problem by encoding the test stimulus using a pseudo-random sequence. The trade-off between the level of rejection of a perturbation and the overall test time is studied. In the case of the MEMS accelerometer considered in this paper, it is demonstrated that the rejection is more than 20dB for a test time of 2.55s. Furthermore, excessively strong perturbations can be monitored so that the test status is updated only if the accuracy of the test signal permits so. It is shown that the proposed solution is compatible with the technique that consists of injecting the stimulus through the sensor bias for the case study MEMS accelerometer.

Published
2007

15. Palliation of malignant gastric outlet obstruction with self-expanding metal stents

Author

Feretis, C Benakis, P Dimopoulos, C Georgopoulos, K and Milas, F Manouras, A Apostolidis, N

Subjects
surgical procedures, operative, cardiovascular diseases, equipment and supplies
Abstract

Background and Study Aims: Self-expanding metal stents have long been used in the management of patients with malignant eosphageal and malignant biliary obstruction, The aim of the present study was to report on the palliation of malignant gastric outlet obstruction using self-expanding endoprostheses. Patients and Methods: Between March 1993 and December 1994, 12 patients (eight women, four men, mean age 64 years) suffering from malignant gastric outlet obstruction due to recurrent gastric carcinoma (seven patients) and pancreatic head carcinoma (five patients) presented with an inability to eat and intractable vomiting, The patients were managed with peroral insertion of self-expanding metal stents. Results: Peroral introduction of the stent with the aid of a stabilizing overtube was successful in all patients, with the stent being supported as it was being advanced through the stenosis, Proper release of the stent into the stenotic area was achieved in all cases, relieving the intractable vomiting, The procedure was accomplished without any complications. All patients were able to eat semisolid food four days after the stent insertion, Apart from an asymptomatic partial stent occlusion in one patient, no other complications were seen during the shortterm follow-up one, two, and three months after discharge, Conclusions: These preliminary results suggest that self-expanding stents can effectively relieve malignant gastric outlet obstruction.

Published
1996

16. Palliation of large-bowel obstruction due to recurrent rectosigmoid tumor using self-expandable endoprostheses

Author

Feretis, C Benakis, P Dimopoulos, C Georgopoulos, K and Manouras, A Apostolidis, N

Abstract

When large-bowel obstruction supervenes in patients ,vith rectal tumor recurrence and extensive nonresectable disease, a proximal diverting colostomy may be indicated. In this study, nonsurgical palliation of the obstruction was attempted by inserting self-expandable endoprostheses to bridge the stenotic lesion. The endoprostheses were positioned in two patients with large-bowel obstruction due to recurrent stenotic tumor, and extensive disease excluding palliative resection. Self-expandable endoprostheses with inner diameters of 18 mm and 22 mm were successfully inserted under endoscopic and radiographic control. Proper expansion of the endoprostheses was achieved in both patients, resulting in immediate decompression of the bowel and lasting relief of the obstruction.

Published
1996

23. Pre-T cell receptor (TCR) and TCR-controlled checkpoints in T cell differentiation are set by Ikaros.

Author

Winandy, S, Wu, L, Wang, JH, Georgopoulos, K, Winandy, S, Wu, L, Wang, JH, and Georgopoulos, K

Abstract

T cell differentiation relies on pre-T cell receptor (TCR) and TCR signaling events that take place at successive steps of the pathway. Here, we show that two of these T cell differentiation checkpoints are regulated by Ikaros. In the absence of Ikaros, double negative thymocytes can differentiate to the double positive stage without expression of a pre-TCR complex. Subsequent events in T cell development mediated by TCR involving transition from the double positive to the single positive stage are also regulated by Ikaros. Nonetheless, in Ikaros-deficient thymocytes, the requirement of pre-TCR expression for expansion of immature thymocytes as they progress to the double positive stage is still maintained, and the T cell malignancies that invariably arise in the thymus of Ikaros-deficient mice are dependent on either pre-TCR or TCR signaling. We conclude that Ikaros regulates T cell differentiation, selection, and homeostasis by providing signaling thresholds for pre-TCR and TCR.

Published
1999

34. Control of lymphocyte development by the Ikaros gene family

Author

Cortes, M., Wong, E., Koipally, J., and Georgopoulos, K.

Abstract

Lymphoid cell differentiation relies on precisely orchestrated gene activation and repression events. Gene targeting studies have demonstrated crucial roles for the transcription factors Ikaros and Aiolos in regulating multiple stages of B and T cell development. Recent experiments suggest that Ikaros and Aiolos set B cell antigen-receptor (BCR)- and TCR-mediated signaling thresholds and that the molecules exist within T cells in nuclear complexes that contain nucleosome remodeling and histone deacetylase activities.

Published
1999
Full Text
View/download PDF

35. A T cell‐specific enhancer is located in a DNase I‐hypersensitive area at the 3′ end of the CD3‐delta gene.

Author

Georgopoulos, K., van den Elsen, P., Bier, E., Maxam, A., and Terhorst, C.

Abstract

During intrathymic differentiation, the genes coding for the T cell receptor/CD3 (TCR/CD3) complex are expressed in stages resulting in surface expression of competent receptors on the most mature T cells. The CD3‐delta, gamma and epsilon proteins, which are expressed intracellularly in the earliest detectable cells of T lineage, form the core of the TCR/CD3 complex. In the present investigation aimed at understanding the tissue specific expression of the murine CD3‐delta gene, a T cell specific DNase I hypersensitive site was found 0.6 kb downstream of the polyadenylation site of the gene. A 0.4 kb genomic fragment encompassing this hypersensitive site exhibited properties of a strictly T cell‐specific transcriptional enhancer which acts in a position‐ and orientation‐independent manner. However, the activity of the promoter region was not found to be T cell restricted. Within this novel T cell‐specific enhancer region, sequence motifs were found which are shared with the promoters of both the mouse and human CD3‐delta genes; in this region we also found sequence homologies to the enhancer core element of the thymotropic viruses SL3 and RadLV. These findings suggest that regulatory elements 3′ of the CD3‐delta gene are at least in part responsible for its exclusive expression in thymus‐derived lymphocytes.

Published
1988
Full Text
View/download PDF

36. Exon/intron organization of the genes coding for the delta chains of the human and murine T-cell receptor/T3 complex.

Author

van den Elsen, P, Georgopoulos, K, Shepley, B A, Orkin, S, and Terhorst, C

Abstract

Genomic DNA clones containing the gene coding for the 20-kDa T3 glycoprotein of the T-cell receptor/T3 complex (T3-delta chain) of human and mouse were isolated and characterized. The human T3-delta gene is approximately equal to 4 kilobases (kb) long and contains five exons: a 151-base-pair (bp) exon containing the 5' untranslated and the coding sequences of the signal peptide, one exon of 219 bp, which contains most of the extracellular segment of the T3-delta chain, one 130-bp-long exon coding mainly for the transmembrane portion of the molecule, and two exons of 44 bp and 156 bp encoding the cytoplasmic domain and 3' untranslated region of the T3-delta chain, respectively. The murine T3-delta gene, which has a similar organization, contains 5 kb, because the first intron is approximately equal to 1 kb larger than in the human gene. Two major mRNA initiation sites within a small area approximately equal to 100 nucleotides 5' of the AUG codon were determined by S1 nuclease analysis and primer-extension studies. The remarkably high level of conservation of nucleotide sequences in this region suggests that this segment may be important for the regulation of T-cell-specific transcription of the T3-delta gene. The T3-delta gene does not contain the "TATA box" found in many eukaryotic promoters.

Published
1986
Full Text
View/download PDF

37. Close linkage of the mouse and human CD3 gamma- and delta-chain genes suggests that their transcription is controlled by common regulatory elements.

Author

Saito, H, Koyama, T, Georgopoulos, K, Clevers, H, Haser, W G, LeBien, T, Tonegawa, S, and Terhorst, C

Abstract

Antigen receptors on the T-cell surface are noncovalently associated with at least four invariant polypeptide chains, CD3-gamma, -delta, -epsilon, and -zeta. The mouse CD3-gamma gene, consisting of seven exons, was found to be highly homologous to the CD3-delta gene described earlier. Both the high level of sequence homology and the exon/intron organization indicate that the CD3-gamma and -delta genes arose by gene duplication. Surprisingly, murine and human genomic DNA clones could be isolated that contained elements of both the CD3-gamma and CD3-delta genes. In fact, the putative transcription start site of the mouse CD3-gamma gene is less than 1.4 kilobases from the transcription initiation site of the mouse CD3-delta gene. Common elements that regulate the divergent transcription of the two genes are therefore proposed to be located in the intervening 1.4-kilobase DNA segment. This might contribute to the coordinate expression of the CD3-gamma and -delta genes during intrathymic maturation of T lymphocytes.

Published
1987
Full Text
View/download PDF

38. Characterization and expression of the murine CD3-epsilon gene.

Author

Clevers, H, Dunlap, S, Saito, H, Georgopoulos, K, Wileman, T, and Terhorst, C

Abstract

The receptor for antigen on the surface of T lymphocytes consists of a variable disulfide-bridged hetero-dimer (TCR-alpha/beta or -gamma/delta) associated with invariant CD3 proteins (CD3-gamma, -delta, -epsilon, and -zeta). The genes coding for the CD3 proteins are expressed in the earliest recognizable thymocytes, preceding the rearrangement and expression of the TCR genes. The isolation, characterization, and in vitro expression of the murine CD3-epsilon gene, as reported here, represent obligatory steps toward our understanding of the complex rules that govern T-cell-specific gene expression. The CD3-epsilon gene was transcribed from a non-TATA promoter and consisted of eight exons, two of which were unusually small (18 and 15 base pairs). The transmembrane exon was found to be homologous to the transmembrane exons of the CD3-gamma and CD3-delta genes. In transient-transfection experiments, a genomic fragment comprising 4 kilobases of upstream sequence and extending into the second exon sufficient to drive the expression of a reporter gene in murine T cells.

Published
1988
Full Text
View/download PDF

40. A reinvestigation of the cross-reactivity between Klebsiella and HLA-B27 in the aetiology of ankylosing spondylitis

Author

Georgopoulos, K, Dick, W C, Goodacre, J A, and Pain, R H

Subjects
Antigens, Bacterial, Immune Sera, Enzyme-Linked Immunosorbent Assay, Cross Reactions, Lymphocyte Activation, Cell Line, HLA Antigens, Klebsiella, Humans, Electrophoresis, Polyacrylamide Gel, Spondylitis, Ankylosing, Lymphocytes, HLA-B27 Antigen, Research Article
Abstract

The existence of cross-reactivity between Klebsiella antigens and cells from donors who are HLA-B27 positive and exhibit ankylosing spondylitis (AS) has been reinvestigated. Cells and antisera from different laboratories have been tested together using simultaneously microcytoxicity, chromium release and enzyme linked immunosorbent assays (ELISA). No reproducible interaction has been found. Mitogenic stimulation did not induce cross-reactivity and 'transformation' of B27+AS- cells by Klebsiella culture supernatants failed. Two transformed cell lines from B27+ AS+ donors exhibited specific cross reaction with two anti-Klebsiella antisera but only by chromium release. Immunoprecipitation with these cells and antisera showed the absence of any AS+ -specific antigen. It is concluded that the involvement of Klebsiella in ankylosing spondylitis through simple immunological cross-reactivity or through interaction with HLA-B27 is unlikely.

Published
1985

44. Distinct signals control the hematopoiesis of lymphoid-related dendritic cells

Author

Anne GALY, Christopherson I, Ferlazzo G, Liu G, Spits H, Georgopoulos K, and Other departments

Subjects
Adult, T-Lymphocytes, Immunology, Down-Regulation, Antigens, CD34, Bone Marrow Cells, Receptors, Cell Surface, Biochemistry, Monocytes, Ikaros Transcription Factor, Antigens, CD, Proto-Oncogene Proteins, Humans, Lymphocytes, Cells, Cultured, Stem Cell Factor, Reverse Transcriptase Polymerase Chain Reaction, Tumor Necrosis Factor-alpha, Interleukins, Macrophages, Granulocyte-Macrophage Colony-Stimulating Factor, Receptor Protein-Tyrosine Kinases, Cell Differentiation, Zinc Fingers, Cell Biology, Hematology, Dendritic Cells, Flow Cytometry, Hematopoietic Stem Cells, Recombinant Proteins, Hematopoiesis, DNA-Binding Proteins, fms-Like Tyrosine Kinase 3, Cytokines, Neprilysin, Signal Transduction, Transcription Factors
Abstract

The molecular and cellular requirements for the development of different populations of human dendritic cells (DC) were studied. Conditions were defined that support DC production from lymphoid progenitors but that fail to induce DC formation from peripheral monocytes. The production of these lymphoid-related DC was severely blocked when hematopoietic progenitors overexpressed Ik7, a mutant dominant-negative Ikaros protein. In contrast, Ik7 did not block the formation of DC in conditions supporting the development of monocyte-derived DC. Furthermore, Ik7 did not block the formation of monocyte/macrophages and enhanced granulopoiesis. One of the molecular mechanisms mediated by Ik7 appears to be down-regulation of the flt3-receptor mRNA. Thus, distinct signals control the formation of DC demonstrating that some aspects of DC diversity are determined in part by distinct molecular cues at the hematopoietic level. (Blood. 2000;95:128-137)

45. The Ikaros gene encodes a family of lymphocyte-restricted zinc finger DNA binding proteins, highly conserved in human and mouse

Author

Molnar, A., Wu, P., Largespada, Da, Vortkamp, A., Stephen W. Scherer, Copeland, Ng, Jenkins, Na, Bruns, G., and Georgopoulos, K.

Subjects
Immunology, Immunology and Allergy
Abstract

The Ikaros gene is an essential regulator in the development and homeostasis of the mouse lymphopoietic system. To study the role of the Ikaros gene in the human lymphopoietic system, we cloned and characterized human Ikaros cDNAs. In the human, as in the mouse, differential splicing of Ikaros primary transcripts generates a family of lymphoid-restricted zinc finger DNA binding proteins, highly conserved in sequence composition and relative expression to the mouse homologues. Expression of Ikaros isoforms is highly restricted to the lymphopoietic system and is particularly enriched in maturing thymocytes. The Ikaros gene maps at a syntenic locus located on the short arm of human chromosome 7 and on mouse chromosome 11 next to the epidermal growth factor receptor (Egfr). The high degree of conservation of the Ikaros gene at the genetic and expression levels strongly suggests that it plays a fundamental role in the ontogeny of the lymphopoietic system across species.

48. Transcription factor Ikzf1 associates with Foxp3 to repress gene expression in Treg cells and limit autoimmunity and anti-tumor immunity.

Author

Ichiyama K, Long J, Kobayashi Y, Horita Y, Kinoshita T, Nakamura Y, Kominami C, Georgopoulos K, and Sakaguchi S

Subjects
Humans, Animals, Mice, Gene Expression Regulation, Mice, Knockout, Neoplasms immunology, Neoplasms genetics, Mice, Inbred C57BL, E1A-Associated p300 Protein metabolism, Ikaros Transcription Factor metabolism, Ikaros Transcription Factor genetics, Forkhead Transcription Factors metabolism, Forkhead Transcription Factors genetics, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism, Autoimmunity genetics, Autoimmunity immunology, Interferon-gamma metabolism
Abstract

The master transcription factor of regulatory T (Treg) cells, forkhead box protein P3 (Foxp3), controls Treg cell function by targeting certain genes for activation or repression, but the specific mechanisms by which it mediates this activation or repression under different conditions remain unclear. We found that Ikzf1 associates with Foxp3 via its exon 5 (IkE5) and that IkE5-deficient Treg cells highly expressed genes that would otherwise be repressed by Foxp3 upon T cell receptor stimulation, including Ifng. Treg-specific IkE5-deletion caused interferon-γ (IFN-γ) overproduction, which destabilized Foxp3 expression and impaired Treg suppressive function, leading to systemic autoimmune disease and strong anti-tumor immunity. Pomalidomide, which degrades IKZF1 and IKZF3, induced IFN-γ overproduction in human Treg cells. Mechanistically, the Foxp3-Ikzf1-Ikzf3 complex competed with epigenetic co-activators, such as p300, for binding to target gene loci via chromatin remodeling. Therefore, the Ikzf1 association with Foxp3 is essential for the gene-repressive function of Foxp3 and could be exploited to treat autoimmune disease and cancer., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Published
2024
Full Text
View/download PDF

49. Vitamin D constrains inflammation by modulating the expression of key genes on Chr17q12-21.1.

Author

Kilic A, Halu A, De Marzio M, Maiorino E, Duvall MG, Bruggemann TR, Rojas Quintero JJ, Chase R, Mirzakhani H, Sungur AÖ, Koepke J, Nakano T, Peh HY, Krishnamoorthy N, Abdulnour RE, Georgopoulos K, Litonjua AA, Demay M, Renz H, Levy BD, and Weiss ST

Subjects
Mice, Animals, Humans, Vitamin D pharmacology, Interleukin-2, Inflammation, Th2 Cells, Vitamins, Asthma, Vitamin D Deficiency metabolism, Pneumonia
Abstract

Vitamin D possesses immunomodulatory functions and vitamin D deficiency has been associated with the rise in chronic inflammatory diseases, including asthma (Litonjua and Weiss, 2007). Vitamin D supplementation studies do not provide insight into the molecular genetic mechanisms of vitamin D-mediated immunoregulation. Here, we provide evidence for vitamin D regulation of two human chromosomal loci, Chr17q12-21.1 and Chr17q21.2, reliably associated with autoimmune and chronic inflammatory diseases. We demonstrate increased vitamin D receptor ( Vdr ) expression in mouse lung CD4+ Th2 cells, differential expression of Chr17q12-21.1 and Chr17q21.2 genes in Th2 cells based on vitamin D status and identify the IL-2/Stat5 pathway as a target of vitamin D signaling. Vitamin D deficiency caused severe lung inflammation after allergen challenge in mice that was prevented by long-term prenatal vitamin D supplementation. Mechanistically, vitamin D induced the expression of the Ikzf3 -encoded protein Aiolos to suppress IL-2 signaling and ameliorate cytokine production in Th2 cells. These translational findings demonstrate mechanisms for the immune protective effect of vitamin D in allergic lung inflammation with a strong molecular genetic link to the regulation of both Chr17q12-21.1 and Chr17q21.2 genes and suggest further functional studies and interventional strategies for long-term prevention of asthma and other autoimmune disorders., Competing Interests: AK, AH, MD, EM, MD, TB, JR, RC, HM, AS, JK, TN, HP, NK, RA, KG, AL, MD, HR, BL No competing interests declared, SW receives royalties from UpToDate and is an investor in Histolix, (© 2023, Kilic, Halu et al.)

Published
2024
Full Text
View/download PDF

50. BRWD1 orchestrates small pre-B cell chromatin topology by converting static to dynamic cohesin.

Author

Mandal M, Maienschein-Cline M, Hu Y, Mohsin A, Veselits ML, Wright NE, Okoreeh MK, Yoon YM, Veselits J, Georgopoulos K, and Clark MR

Subjects
Precursor Cells, B-Lymphoid, Gene Expression Regulation, Cell Differentiation, Cell Cycle Proteins genetics, Cell Cycle Proteins metabolism, Cohesins, Chromatin genetics
Abstract

Lymphocyte development consists of sequential and mutually exclusive cell states of proliferative selection and antigen receptor gene recombination. Transitions between each state require large, coordinated changes in epigenetic landscapes and transcriptional programs. How this occurs remains unclear. Here we demonstrate that in small pre-B cells, the lineage and stage-specific epigenetic reader bromodomain and WD repeat-containing protein 1 (BRWD1) reorders three-dimensional chromatin topology to affect the transition between proliferative and gene recombination molecular programs. BRWD1 regulated the switch between poised and active enhancers interacting with promoters, and coordinated this switch with Igk locus contraction. BRWD1 did so by converting chromatin-bound static to dynamic cohesin competent to mediate long-range looping. ATP-depletion revealed cohesin conversion to be the main energetic mechanism dictating dynamic chromatin looping. Our findings provide a new mechanism of cohesin regulation and reveal how cohesin function can be dictated by lineage contextual mechanisms to facilitate specific cell fate transitions., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Published
2024
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results