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Fetal thymus

Shiyun Xiao, Wen Zhang, Nancy R Manley
The postnatal thymus is an efficient microenvironment for T cell specification and differentiation. B cells are also present in the thymus and have been recently shown to impact T cell selection, however, the mechanisms controlling B cell development in the thymus are largely unknown. In Foxn1lacZ mutant mice, down-regulation of Foxn1 expression in thymic epithelial cells beginning 1 week after birth caused a dramatic reduction of T progenitors and an increase of B cell progenitors. This time point is coincident with the switch from fetal to adult-type hematopoietic stem cells (HSCs), which is regulated by the Lin28-Let7 system...
2018: PloS One
Shelley M Lawrence, Ross Corriden, Victor Nizet
Comprising the majority of leukocytes in humans, neutrophils are the first immune cells to respond to inflammatory or infectious etiologies and are crucial participants in the proper functioning of both innate and adaptive immune responses. From their initial appearance in the liver, thymus, and spleen at around the eighth week of human gestation to their generation in large numbers in the bone marrow at the end of term gestation, the differentiation of the pluripotent hematopoietic stem cell into a mature, segmented neutrophil is a highly controlled process where the transcriptional regulators C/EBP-α and C/EBP-ε play a vital role...
June 2018: Microbiology and Molecular Biology Reviews: MMBR
Kristofor K Ellestad, Govindarajan Thangavelu, Yohannes Haile, Jiaxin Lin, Louis Boon, Colin C Anderson
Lymphopenia can result from various factors, including viral infections, clinical interventions, or as a normal property of the fetal/neonatal period. T cells in a lymphopenic environment undergo lymphopenia-induced proliferation (LIP) to fill the available "niche" as defined by peptide-MHC and homeostatic cytokine resources. We recently reported systemic autoimmunity following reconstitution of the lymphoid compartment of Rag1-/- mice with PD-1-/- hematopoietic stem cells or by transfer of thymocytes, but not splenocytes, suggesting that programmed death-1 (PD-1) plays a crucial role in controlling recent thymic emigrants (RTE) and preventing autoimmunity upon their LIP...
2018: Frontiers in Immunology
Anisha Solanki, Diana C Yanez, Susan Ross, Ching-In Lau, Eleftheria Papaioannou, Jiawei Li, José Ignacio Saldaña, Tessa Crompton
Gli3 is a Hedgehog (Hh) responsive transcription factor that can function as a transcriptional repressor or activator. We show that Gli3 activity in thymic epithelial cells (TEC) promotes positive selection and differentiation from CD4+CD8+ to CD4+CD8- single positive (SP4) cell in the fetal thymus and that Gli3 represses Shh Constitutive deletion of Gli3, and conditional deletion of Gli3 from TEC, reduced differentiation to SP4, whereas conditional deletion of Gli3 from thymocytes did not. Conditional deletion of Shh from TEC increased differentiation to SP4, and expression of Shh was upregulated in the Gli3-deficient thymus...
January 18, 2018: Development
Rafael Dos Santos de Andrade, Frederico Ozanan Barros Monteiro, Hani Rocha El Bizri, Wilter Ricardo Russiano Vicente, Diva Anelie de Araujo Guimarães, Pedro Mayor
The intrauterine development is an evolutionary strategy that prepares the neonate for extra-uterine life, thus providing important information on the life history of species. In this study, we described the external and internal morphology of 25 fetuses of Poeppig's woolly monkeys (Lagothrix poeppigii) by taking advantage of a 10-year participatory collection of biological samples originated from animals hunted for subsistence purposes in the Peruvian Amazon. Logistic regressions estimated the probability of occurrence of each external morphological characteristic in relation to the crown-rump length (CRL)...
December 8, 2017: Theriogenology
N V Lifantseva, Ts O Koneeva, E E Voronezhskaya, V I Melnikova
The developing thymus of rat fetuses contains all components of the serotonergic system: receptors, enzymes of synthesis, and membrane transporters. The expression of receptors suggests the possibility of a direct influence of serotonin on thymic development. The presence of tryptophan hydroxylase (the key rate-limiting enzyme of serotonin synthesis) and aromatic l-amino acid decarboxylase indicates the ability of fetal thymic cells to synthesize serotonin. It was shown that the cells of a developing thymus can actively uptake extracellular monoamines...
November 2017: Doklady. Biochemistry and Biophysics
Wolf Wippermann, Anne Heckmann, Kathrin Jäger, Sven Dänicke, Heinz-Adolf Schoon
In order to evaluate the influence of deoxynivalenol (DON) on histomorphological and immunohistochemical parameters in the development of porcine fetuses, five pregnant sows were fed a control diet (0.15 mg DON/kg diet) and seven sows a contaminated diet (4.42 mg DON/kg diet) between days 35 and 70 of gestation. On day 70, fetuses were delivered by caesarean section and sows and fetuses were euthanized. Tissue samples of three fetuses from each sow were collected, fixed in formalin, and processed routinely for light microscopy and immunohistochemistry...
December 29, 2017: Mycotoxin Research
Pedro H Papotto, Annika Reinhardt, Immo Prinz, Bruno Silva-Santos
IL-17-producing γδ (γδ17) T cells form a versatile subset of cells that respond rapidly to innate stimuli and support the pro-inflammatory functions of different myeloid and lymphoid lineages, being particularly critical in the early stages of inflammatory and autoimmune responses. In mice, under homeostatic conditions, these innate-like lymphocytes are pre-programmed in the fetal thymus, through an intricate process involving both T cell receptor-dependent and -independent signals, which allows them to readily produce IL-17 upon stimulation...
February 2018: Journal of Autoimmunity
M P Chrysouli, C N Banti, N Kourkoumelis, N Panayiotou, G S Markopoulos, A J Tasiopoulos, S K Hadjikakou
The antiproliferative activity of the gold complex [Au(tpp)Cl] (1) (tpp=triphenyphosphine) against human breast adenocarcinoma cells (MCF-7) and normal human fetal lung fibroblast cells (MRC-5) was investigated. The compound exhibits stronger activity against MCF-7 cells than cisplatin. The apoptotic pathway, especially though the mitochondrion damage was concluded by cell cycle arrest, flow cytometry using Annexin V-Fluorescein IsoThioCyanate (FITC) and Propidium Iodide (PI) as indicators, assays and permeabilization of the mitochondrial membrane tests...
February 2018: Journal of Inorganic Biochemistry
Guillemette Masse-Ranson, Hugo Mouquet, James P Di Santo
PURPOSE OF REVIEW: Immunodeficient mice that lack all lymphocyte subsets and have phagocytic cells that are tolerant of human cells can be stably xenografted with human hematopoietic stem cell as well as other human tissues (fetal liver and thymus) creating 'human immune system' (HIS) mice. HIS mice develop all major human lymphocyte classes (B, T, natural killer, and innate lymphoid cell) and their specialized subsets as well as a variety of myeloid cells (dendritic cell, monocytes, and macrophages) thereby providing a small animal model in which to interrogate human immune responses to infection...
March 2018: Current Opinion in HIV and AIDS
Pengfei Chen, Haohao Zhang, Xiaohua Sun, Yiming Hu, Wenxia Jiang, Zhanjie Liu, Sanhong Liu, Xiaoren Zhang
Medullary thymic epithelial cells (mTECs) ectopically express a diversity of peripheral tissue-restricted antigens (PTAs) and provide unique cues for the expansion, maturation and selection of a repertoire of functionally diverse T lymphocytes. Genetic deletion of all mature microRNAs in thymic epithelial cells (TECs) results in premature thymic involution, progressive disorganisation of the thymic epithelium, and alteration in thymic T cell lineage commitment, consequently eliciting autoimmune disorders. In the present study, we identified that microRNA-449a (miR-449a), a member of miR-449 cluster, regulated mTEC differentiation...
November 21, 2017: Scientific Reports
Katharina Warncke, Ramona Lickert, Stephanie Eitel, Karl-Philipp Gloning, Ezio Bonifacio, Eva-Maria Sedlmeier, Petra Becker, Jan Knoop, Andreas Beyerlein, Anette-Gabriele Ziegler
Type 1 diabetes (T1D) during pregnancy possibly affects the development of the thymus and the maturation of the immune system in the offspring. The aim of the ImmunDiabRisk study was to investigate thymus growth and maternal and fetal immune responses in pregnancies with and without T1D. The thymus circumferences of the fetuses of pregnant women with T1D (n=49) and without diabetes (n=59) were measured using ultrasound around the 29th gestational week and standardized for gestational age. Simultaneously, the frequencies and total numbers of cell markers were analyzed by flow cytometry in maternal peripheral blood, and at birth in umbilical cord blood...
November 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
Christina N Banti, Constantina Papatriantafyllopoulou, Anastasios J Tasiopoulos, Sotiris K Hadjikakou
The non steroidal anti-inflammatory drugs (NSAID's)-silver(I) metallodrugs of aspirin (aspH), salicylic acid (salH2), naproxen (napH) acid or p-hydrobenzoic acid (pHbzaH) and the mitochondriotropic triphenylarsine (tpAs) with the formulae [Ag(asp)(tpAs)3] (1), [Ag(salH)(tpAs)3] (2), [Ag(nap)(tpAs)3] (3) and {[Ag(pHbza)(tpAs)3]∙(dmf)} (4) and [Ag(tpAs)3(NO3)] (5) have been synthesized and characterized by m.p., FT-IR, UV-vis and (1)H NMR, spectroscopic techniques and X-ray crystallography. The in vitro cytotoxic activity of 1-5 against human breast adenocarcinoma cancer cells: MCF-7 (positive to estrogen receptors (ERs)) and MDA-MB-231 (negative to estrogen receptors (ERs)) was evaluated...
November 10, 2017: European Journal of Medicinal Chemistry
Shinya Hatano, Tesshin Murakami, Naoto Noguchi, Hisakata Yamada, Yasunobu Yoshikai
We recently found that a unique subset of innate-like γδ T cells develops from the DN2a stage of the fetal thymus independently of the zinc-finger transcription factor B cell leukemia/lymphoma 11b (Bcl11b). Herein, we characterize these Bcl11b-independent γδ T cells in the periphery as CD5(-)NK1.1(+) and Granzyme B(+), and we show that they are capable of producing interferon (IFN)-γ upon T cell receptor stimulation without Ca(2+) influx. In wild-type mice, these cells were sparse in lymphoid tissues but abundant in non-lymphoid tissues, such as the liver...
October 31, 2017: Cell Reports
Ge Zhao, Jing Liu, Tao Meng
OBJECTIVES: The aim of this study was to assess the correlation between the thymic-thoracic ratio and cardiac axis in healthy fetuses. METHODS: The fetal thymic-thoracic ratio and cardiac axis were measured in 220 healthy fetuses. The normal ranges of the fetal thymic-thoracic ratio and cardiac axis for each gestational week were established. The Pearson correlation coefficient was calculated to analyze the relationship between the thymic-thoracic ratio and cardiac axis...
October 24, 2017: Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine
Claudia Caissutti, Alessandra Familiari, Asma Khalil, Maria E Flacco, Lamberto Manzoli, Giovanni Scambia, Angelo Cagnacci, Francesco D'antonio
INTRODUCTION: The aim of this study was to explore the association between small fetal thymus on ultrasound and adverse obstetrical outcome. MATERIAL AND METHODS: Medline, Embase, Cochrane and Web of Science databases were searched. Primary outcome was the risk of preterm birth before 37 and 34 weeks of gestation in fetuses with, compared to those without, a small thymus on ultrasound. SECONDARY OUTCOMES: occurrence of chorioamnionitis, intrauterine growth restriction, neonatal sepsis, gestational age at birth, birthweight, neonatal morbidity and preeclampsia...
February 2018: Acta Obstetricia et Gynecologica Scandinavica
Vincent Geenen
This synthesis presents the most important disruptions of conceptions about the thymus since its discovery in Antique Greece. For centuries, the thymus was considered as a vestigial organ, and its role in T-lymphocyte differentiation has been proposed only in the 1960's. Most recent studies attribute to the thymus an essential and unique role in the programming of central immunological self-tolerance. The basal mechanism implicated in this function is the transcription in thymic epithelium of genes encoding precursors of self-antigens...
June 2017: Médecine Sciences: M/S
Wen Qu, Liang-Peng Ma, Hui-Yi Yan, Sha Liu, Han-Xiao Liu, Ting Chen, Li-Fang Hou, Jie Ping
This study was designed to observe the effects of maternal food restriction (MFR) on the development of fetal thymus in different gestation periods. Timed pregnant rats were randomized into 3 groups: CN (free access to standard chow throughout gestation), MFR0-21 (50% MFR throughout gestation), MFR0-14 (50% MFR from gestational day (GD) 0 to GD14, early-mid gestation). Results showed that MFR during early-mid period had few impact on the fetal thymus and T cell subpopulations. However, MFR throughout gestation resulted in thymic atrophy, deceased frequency of both CD4(+) and CD8(+) single positive (SP) T cells and enhanced thymocyte apoptosis in fetus...
August 24, 2017: Environmental Toxicology and Pharmacology
Shulian Tan, Yang Li, Jinxing Xia, Chun-Hui Jin, Zheng Hu, Gaby Duinkerken, Yuying Li, Mohsen Khosravi Maharlooei, Estefania Chavez, Grace Nauman, Nichole Danzl, Maki Nakayama, Bart O Roep, Megan Sykes, Yong-Guang Yang
There is an urgent and unmet need for humanized in vivo models of type 1 diabetes to study immunopathogenesis and immunotherapy, and in particular antigen-specific therapy. Transfer of patient blood lymphocytes to immunodeficient mice is associated with xenogeneic graft-versus-host reactivity that complicates assessment of autoimmunity. Improved models could identify which human T cells initiate and participate in beta-cell destruction and help define critical target islet autoantigens. We used humanized mice (hu-mice) containing robust human immune repertoires lacking xenogeneic graft-versus-host reactivity to address this question...
October 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
Pedro H Papotto, Natacha Gonçalves-Sousa, Nina Schmolka, Andrea Iseppon, Sofia Mensurado, Brigitta Stockinger, Julie C Ribot, Bruno Silva-Santos
Pro-inflammatory interleukin (IL)-17-producing γδ (γδ17) T cells are thought to develop exclusively in the thymus during fetal/perinatal life, as adult bone marrow precursors fail to generate γδ17 T cells under homeostatic conditions. Here, we employ a model of experimental autoimmune encephalomyelitis (EAE) in which hematopoiesis is reset by bone marrow transplantation and demonstrate unequivocally that Vγ4+ γδ17 T cells can develop de novo in draining lymph nodes in response to innate stimuli. In vitro, γδ T cells from IL-17 fate-mapping reporter mice that had never activated the Il17 locus acquire IL-17 expression upon stimulation with IL-1β and IL-23...
November 2017: EMBO Reports
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