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Raul Vizcardo, Nicholas D Klemen, S M Rafiqul Islam, Devikala Gurusamy, Naritaka Tamaoki, Daisuke Yamada, Haruhiko Koseki, Benjamin L Kidder, Zhiya Yu, Li Jia, Amanda N Henning, Meghan L Good, Marta Bosch-Marce, Takuya Maeda, Chengyu Liu, Zied Abdullaev, Svetlana Pack, Douglas C Palmer, David F Stroncek, Fumito Ito, Francis A Flomerfelt, Michael J Kruhlak, Nicholas P Restifo
Induced pluripotent stem cell (iPSC)-derived T cells may provide future therapies for cancer patients, but those generated by current methods, such as the OP9/DLL1 system, have shown abnormalities that pose major barriers for clinical translation. Our data indicate that these iPSC-derived CD8 single-positive T cells are more like CD4+ CD8+ double-positive T cells than mature naive T cells because they display phenotypic markers of developmental arrest and an innate-like phenotype after stimulation. We developed a 3D thymic culture system to avoid these aberrant developmental fates, generating a homogeneous subset of CD8αβ+ antigen-specific T cells, designated iPSC-derived thymic emigrants (iTEs)...
March 20, 2018: Cell Reports
Martine J Kallemeijn, François G Kavelaars, Michèle Y van der Klift, Ingrid L M Wolvers-Tettero, Peter J M Valk, Jacques J M van Dongen, Anton W Langerak
Immunological aging remodels the immune system at several levels. This has been documented in particular for the T-cell receptor (TCR)αβ+ T-cell compartment, showing reduced naive T-cell outputs and an accumulation of terminally differentiated clonally expanding effector T-cells, leading to increased proneness to autoimmunity and cancer development at older age. Even though TCRαβ+ and TCRγδ+ T-cells follow similar paths of development involving V(D)J-recombination of TCR genes in the thymus, TCRγδ+ T-cells tend to be more subjected to peripheral rather than central selection...
2018: Frontiers in Immunology
Nuray Erin, Nur Ogan, Azmi Yerlikaya
PURPOSE: Metastatic breast cancer is resistant to many conventional treatments and novel therapeutic targets are needed. We previously isolated subsets of 4T1 murine breast cancer cells which metastasized to liver (4TLM), brain (4TBM), and heart (4THM). Among these cells, 4TLM is the most aggressive one, demonstrating mesenchymal phenotype. Here we compared secreted proteins from 4TLM, 4TBM, and 4THM cells and compared with that of hardly metastatic 67NR cells to detect differentially secreted factors involved in organ-specific metastasis...
March 20, 2018: Breast Cancer Research and Treatment
Chuang Qu, Shuhui Gao, Hongwei Shao, Wenfeng Zhang, Huabben Bo, Xin Lu, Tianjiao Chen, Jing Kou, Yue Wang, Gui Si Chen, Shulin Huang, Han Shen
Cluster of differentiation (CD)147 is highly expressed in drug-resistant tumor cell lines and is involved in the formation of tumor drug resistance. Therefore, immunotherapy utilizing CD147 epitope peptides is a promising approach for the elimination of drug-resistant tumor cells. However, like most tumor-associated antigens (TAAs), CD147 belongs to the autoantigen category, and T cells that recognize high affinity, immunodominant epitopes from autoantigens are deleted though thymic negative selection. Furthermore, wild-type autoantigen peptides cannot effectively activate and expand T lymphocytes with lower affinity T cell receptors in vivo ...
April 2018: Oncology Letters
Yong Jing, Wei-Qiang Yan, Gang-Feng Li, Shi-Jun Duan, Shu-Mei Wang, Lin Sun, Yu-Chuan Hu, Guang-Bin Cui
PURPOSE: This study aimed to evaluate the usefulness of volume perfusion computed tomography (VPCT) parameters in differentiating the World Health Organization subtypes of thymic epithelial tumors. MATERIALS AND METHODS: This study was approved by the local ethics committee, and informed written consent was obtained. Fifty-one thymic epithelial tumor patients confirmed by histopathological analysis underwent conventional CT and a 48-second VPCT scan of the tumor bulk before any treatment...
March 16, 2018: Journal of Computer Assisted Tomography
Narges Aghaallaei, Baubak Bajoghli
T-cell development is coupled with a highly ordered migratory pattern. Lymphoid progenitors must follow a precise journey; starting from the hematopoietic tissue, they move toward the thymus and then migrate into and out of distinct thymic microenvironments, where they receive signals and cues required for their differentiation into naïve T-cells. Knowing where, when, and how these cells make directional "decisions" is key to understanding T-cell development. Such insights can be gained by directly observing developing T-cells within their environment under various conditions and following specific experimental manipulations...
2018: Frontiers in Immunology
Sujun Sun, Haiyu Ji, Yingying Feng, Yu Kang, Juan Yu, Anjun Liu
Background: Thymic atrophy was discovered in tumor-bearing mice in recent years. Methods: Flow cytometry was carried out including Annexin V-FITC/PI double staining, PI staining, Terminal dUTP nick-end labeling, CD3-FITC/CD19-PE and CD8-FITC/CD4-PE double staining. Enzyme-linked immunosorbent assay and polymerase chain reaction were also investigated. Results: According to our experiments, we demonstrated that no signs of apoptosis in thymocytes were found in H22-bearing mice, while the proportions of CD4+ T cells and CD8+ T cells in thymuses were remarkably increased, the opposite tendency was found in peripheral bloods, and only CD3+ CD8+ T cells were discovered in H22 solid tumors...
2018: Cancer Management and Research
Lin Sun, Chenyang Dai, Jiayin Wu, Chen Chen, Xinyi Wu
Thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine, which is secreted by epithelial cells under the stimulation of Toll-like receptor (TLR) ligands. Dendritic cells (DCs) which express the thymic stromal lymphopoietin receptor (TSLPR) can be activated by TSLP. Mature DCs can express the OX40 ligand, which has the ability to combine with OX40 on the surface of T cells to stimulate T cell proliferation. TSLP secreted by corneal epithelial cells can engage in the process of T helper type 2 (Th2) inflammation in Aspergillus fumigatus keratitis, but the mechanism remains unclear...
March 14, 2018: Experimental Eye Research
Andrea Farolfi, Francesco Ceci, Tiziano Graziani, Alessandro Lambertini, Veronica Cervati, Gian Luca Basilico, Tullio Biraghi, Alberto Briganti, Paolo Castellucci, Stefano Fanti
No abstract text is available yet for this article.
February 23, 2018: Clinical Genitourinary Cancer
Vasiliki Zouvelou, Efstratios Karavasilis, Georgios Velonakis
No abstract text is available yet for this article.
February 26, 2018: Neuromuscular Disorders: NMD
Thomas Joshua Pasvol, Caroline Foster, Sarah Fidler
PURPOSE OF REVIEW: Successful roll-out of paediatric antiretroviral therapy (ART) has led to a significant increase in survival of adolescents and young people growing up with HIV. Those on suppressive ART since childhood represent a unique group particularly well positioned to interrupt ART and achieve post-treatment control (PTC), or HIV remission. This maybe a consequence of early and sustained treatment since infancy, the small size of the HIV reservoir, the presence of a functioning thymus and a more 'flexible' immune system better able to respond to novel immune therapeutic interventions when compared with adults who acquired HIV at a time of immunological maturity and thymic involution...
March 14, 2018: Current Opinion in HIV and AIDS
Di Wang, Qian Li, Yidi Qu, Mengya Wang, Lanzhou Li, Yang Liu, Yu Li
Gloeostereum incarnatum , a precious edible mushroom, displays anti-bacterial and anti-inflammatory activities; however, its immunomodulatory effect has not been studied yet. The present study aimed to investigate whether polysaccharide compositions of G. incarnatum polysaccharides (GIPS) possess immunomodulatory and immuno-enhancing effects in a Cyclophosphamide monohydrate (CTX)-induced BALB/c mice model. The 28-day GIPS administration at doses of 0.1, 0.3 and 0.9 g/kg remarkably reversed the bodyweight loss, increased the thymic index and promoted T lymphocyte proliferation in CTX-induced immunosuppressed mice...
April 2018: Experimental and Therapeutic Medicine
Mizuki Ikeda, Junji Deguchi, Shota Fukushima, Ai Qingyu, Norihiro Katayama, Hajime Miura, Yasuo Oyama
Chlorothalonil, a polychlorinated aromatic fungicide, is considered non-toxic to small mammals. However, chlorothalonil inactivates sulfhydryl enzymes and depletes cellular glutathione. Chlorothalonil increases intracellular Zn2+ concentration ([Zn2+ ]i) in mammalian cells possibly because intracellular Zn2+ is released via zinc-thiol/disulfide interchange. The effects of chlorothalonil at sublethal concentrations on the cellular content of nonprotein thiols ([NPT]i) and [Zn2+ ]i were examined using flow cytometry in rat thymocytes...
March 8, 2018: Environmental Toxicology and Pharmacology
Girak Kim, Min Jeong Gu, Soo Ji Kim, Kwang Hyun Ko, Yoon-Chul Kye, Cheol Gyun Kim, Jae-Ho Cho, Woon-Kyu Lee, Ki-Duk Song, Hyuk Chu, Yeong-Min Park, Seung Hyun Han, Cheol-Heui Yun
γδ T cells, known to be an important source of innate IL-17 in mice, provide critical contributions to host immune responses. Development and function of γδ T cells are directed by networks of diverse transcription factors (TFs). Here, we examine the role of the zinc finger TFs, Kruppel-like factor 10 (KLF10), in the regulation of IL-17-committed CD27- γδ T (γδ27- -17) cells. We found selective augmentation of Vγ4+ γδ27- cells with higher IL-17 production in KLF10-deficient mice. Surprisingly, KLF10-deficient CD127hi Vγ4+ γδ27- -17 cells expressed higher levels of CD5 than their wild-type counterparts, with hyper-responsiveness to cytokine, but not T-cell receptor, stimuli...
2018: Frontiers in Immunology
Lauren A Bruns, Sarah Isbey, Melisa Tanverdi, Ian Kane
Although there are several reports of intracranial hemorrhage associated with vitamin K deficient bleeding, there are few reported cases of extracranial manifestations, specifically involving the thymus. Here, we discuss the unique case of a 4-week-old infant presenting with scrotal discoloration, respiratory distress, and widened mediastinum, found to have thymic hemorrhage related to confirmed coagulopathy secondary to late-onset vitamin K deficiency bleeding of the newborn.
March 12, 2018: Pediatric Emergency Care
Hitoshi Hasegawa, Takuya Matsumoto
Dendritic cells (DCs) are a heterogeneous population playing a pivotal role in immune responses and tolerance. DCs promote immune tolerance by participating in the negative selection of autoreactive T cells in the thymus. Furthermore, to eliminate autoreactive T cells that have escaped thymic deletion, DCs also induce immune tolerance in the periphery through various mechanisms. Breakdown of these functions leads to autoimmune diseases. Moreover, DCs play a critical role in maintenance of homeostasis in body organs, especially the skin and intestine...
2018: Frontiers in Immunology
Yrina Rochman, Krista Dienger-Stambaugh, Phoebe K Richgels, Ian P Lewkowich, Andrey V Kartashov, Artem Barski, Gurjit K Khurana Hershey, Warren J Leonard, Harinder Singh
Pathogenic T helper 2 (TH 2) cells, which produce increased amounts of the cytokines interleukin-5 (IL-5) and IL-13, promote allergic disorders, including asthma. Thymic stromal lymphopoietin (TSLP), a cytokine secreted by epithelial and innate immune cells, stimulates such pathogenic TH 2 cell responses. We found that TSLP signaling in mouse CD4+ T cells initiated transcriptional changes associated with TH 2 cell programming. IL-4 signaling amplified and stabilized the genomic response of T cells to TSLP, which increased the frequency of T cells producing IL-4, IL-5, and IL-13...
March 13, 2018: Science Signaling
Sara A Hayes, James Huang, Jennifer Golia Pernicka, Jane Cunningham, Junting Zheng, Chaya S Moskowitz, Michelle S Ginsberg
BACKGROUND: The aim of this study was to assess pre-operative computed tomography (CT) characteristics of thymic carcinomas and to investigate which features could predict an incomplete surgical resection. A secondary aim was to correlate pre-operative imaging features with Masaoka stage. METHODS: In this study, approved by our Institutional Review Board, two readers retrospectively reviewed pre-operative CTs at our tertiary referral oncology center between 1994 and 2014...
March 10, 2018: Annals of Thoracic Surgery
Yang Wang, Liangliang Xu, Tongxin Du, Yunfei Gao, Zhenhua Wu, Dongbo Luo
BACKGROUND: Resection is an effective treatment for thymic carcinoma. We aimed to develop a nomogram for postoperative prediction of recurrence-free survival (RFS) for patients with thymic carcinoma and guide adjuvant radiotherapy. METHODS: A total of 198 patients who underwent surgery were divided into training (n=152) and validation (n=46) cohorts. Clinicopathologic features and independent factors for postoperative recurrence were analyzed. A predictive nomogram was developed based on the prognostic factors...
March 9, 2018: Annals of Thoracic Surgery
Melda Onal, Alex H Carlson, Jeff D Thostenson, Nancy A Benkusky, Mark B Meyer, Seong M Lee, J Wesley Pike
Fibroblast growth factor 23 (FGF23) production is regulated by both calciotropic hormones and inflammation. Consistent with this, elevated FGF23 levels are associated with inflammatory markers as well as parathyroid hormone (PTH) in various disease states, including chronic kidney disease (CKD). However, the molecular mechanisms underpinning Fgf23 transcription in response to these regulators are largely unknown. We therefore utilized chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) data from an osteocyte cell line to identify potential regulatory regions of the Fgf23 gene...
January 2018: JBMR Plus
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