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https://www.readbyqxmd.com/read/29784760/formation-of-the-intrathymic-dendritic-cell-pool-requires-ccl21-mediated-recruitment-of-ccr7-progenitors-to-the-thymus
#1
Emilie J Cosway, Izumi Ohigashi, Karin Schauble, Sonia M Parnell, William E Jenkinson, Sanjiv Luther, Yousuke Takahama, Graham Anderson
During αβ T cell development in the thymus, migration of newly selected CD4+ and CD8+ thymocytes into medullary areas enables tolerance mechanisms to purge the newly selected αβ TCR repertoire of autoreactive specificities. Thymic dendritic cells (DC) play key roles in this process and consist of three distinct subsets that differ in their developmental origins. Thus, plasmacytoid DC and Sirpα+ conventional DC type 2 are extrathymically derived and enter into the thymus via their respective expression of the chemokine receptors CCR9 and CCR2...
May 21, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29782660/the-feared-five-fungal-infections-in-kidney-transplant-recipients-a-single-center20-year-experience
#2
Sandesh Parajuli, Alexandra Wick, Sameer Pandeya, Brad C Astor, Jeannina Smith, Arjang Djamali, Didier A Mandelbrot
Invasive fungal infections are a feared complication in kidney transplant recipients (KTRs). Here we present the University of Wisconsin experience with five invasive fungal infections - aspergillosis, cryptococcosis, histoplasmosis, blastomycosis, and coccidioidomycosis - in KTRs transplanted between 01/01/1994 and 06/30/2014. During this period there were 128 cases of fungal infections; aspergillosis was the most common (72), followed by cryptococcosis (29), histoplasmosis (14), blastomycosis (10) and coccidioidomycosis (3)...
May 21, 2018: Clinical Transplantation
https://www.readbyqxmd.com/read/29781553/effects-of-melatonin-on-thymic-and-oxidative-stress-dysfunctions-during-trypanosoma-cruzi-infection
#3
Vânia Brazão, Rafaela Pravato Colato, Fabricia Helena Santello, Gabriel Tavares do Vale, Natália de Almeida Gonzaga, Carlos Renato Tirapelli, José Clóvis do Prado
Although the exact etiology of Chagas' disease is not completely elucidated, thymic atrophy and oxidative stress are believed to be important contributors to the pathogenesis during acute Trypanosoma cruzi (T. cruzi) infection. We hypothethized that exogenous melatonin, administered by gavage (5 mg/kg, p.o., gavage) to young (5 weeks old) and middle-aged (18 months old) male Wistar rats would modulate thymic oxidative damage and reverse the age-related thymus regression during T. cruzi acute infection. Increased levels of superoxide anion (O2 - ) were detected in the thymus of infected animals and treatment with melatonin reverted this response...
May 21, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29780388/regulation-of-hematopoietic-cell-development-and-function-through-phosphoinositides
#4
REVIEW
Mila Elich, Karsten Sauer
One of the most paramount receptor-induced signal transduction mechanisms in hematopoietic cells is production of the lipid second messenger phosphatidylinositol(3,4,5)trisphosphate (PIP3 ) by class I phosphoinositide 3 kinases (PI3K). Defective PIP3 signaling impairs almost every aspect of hematopoiesis, including T cell development and function. Limiting PIP3 signaling is particularly important, because excessive PIP3 function in lymphocytes can transform them and cause blood cancers. Here, we review the key functions of PIP3 and related phosphoinositides in hematopoietic cells, with a special focus on those mechanisms dampening PIP3 production, turnover, or function...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29775646/the-rna-binding-protein-ars2-supports-hematopoiesis-at-multiple-levels
#5
Seerat Elahi, Shawn M Egan, G Aaron Holling, Rachel L Kandefer, Michael J Nemeth, Scott H Olejniczak
Recent biochemical characterization of Arsenic resistance protein 2 (Ars2) has established it as central to determining the fate of nascent RNA polymerase II (RNAPII) transcripts. Through interactions with the nuclear 5'-7-methylguanosine (7mG) cap binding complex (CBC), Ars2 promotes co-transcriptional processing coupled with nuclear export or degradation of several classes of RNAPII transcripts, allowing for gene expression programs that facilitate rapid and sustained proliferation of immortalized cells in culture...
May 15, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29775115/immunofluorescent-localization-of-non-myelinating-schwann-cells-and-their-interactions-with-immune-cells-in-mouse-thymus
#6
Dailun Hu, Philip K Nicholls, Changfu Yin, Khama Kelman, Qionglan Yuan, Wayne K Greene, Zhongli Shi, Bin Ma
The thymus is innervated by sympathetic/parasympathetic nerve fibers from the peripheral nervous system (PNS), suggesting a neural regulation of thymic function including T-cell development. Despite some published studies, data on the innervation and nerve-immune interaction inside the thymus remain limited. In the present study, we used immunofluorescent staining of glial fibrillary acidic protein (GFAP) coupled with confocal microscopy/three-dimensional (3D) reconstruction to reveal the distribution of non-myelinating Schwann cells (NMSC) and their interactions with immune cells inside mouse thymus...
May 1, 2018: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/29765355/tuberculosis-the-disrupted-immune-endocrine-response-and-the-potential-thymic-repercussion-as-a-contributing-factor-to-disease-physiopathology
#7
REVIEW
Luciano D'Attilio, Natalia Santucci, Bettina Bongiovanni, María L Bay, Oscar Bottasso
Upon the pathogen encounter, the host seeks to ensure an adequate inflammatory reaction to combat infection but at the same time tries to prevent collateral damage, through several regulatory mechanisms, like an endocrine response involving the production of adrenal steroid hormones. Our studies show that active tuberculosis (TB) patients present an immune-endocrine imbalance characterized by an impaired cellular immunity together with increased plasma levels of cortisol, pro-inflammatory cytokines, and decreased amounts of dehydroepiandrosterone...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29757216/sphingosine-1-phosphate-receptor-1-is-involved-in-non-obese-diabetic-mouse-thymocyte-migration-disorders
#8
Julia P Lemos, Salete Smaniotto, Carolina V Messias, Otacilio C Moreira, Vinicius Cotta-de-Almeida, Mireille Dardenne, Wilson Savino, Daniella A Mendes-da-Cruz
NOD (non-obese diabetic) mice spontaneously develop type 1 diabetes following T cell-dependent destruction of pancreatic β cells. Several alterations are observed in the NOD thymus, including the presence of giant perivascular spaces (PVS) filled with single-positive (SP) CD4⁺ and CD8⁺ T cells that accumulate in the organ. These cells have a decreased expression of membrane CD49e (the α5 integrin chain of the fibronectin receptor VLA-5 (very late antigen-5). Herein, we observed lower sphingosine-1-phosphate receptor 1 (S1P1) expression in NOD mouse thymocytes when compared with controls, mainly in the mature SP CD4⁺CD62Lhi and CD8⁺CD62Lhi subpopulations bearing the CD49e− phenotype...
May 12, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29753741/long-term-hindlimb-unloading-causes-a-preferential-reduction-of-medullary-thymic-epithelial-cells-expressing-autoimmune-regulator-aire
#9
Kenta Horie, Takashi Kudo, Riko Yoshinaga, Nobuko Akiyama, Hiroki Sasanuma, Tetsuya J Kobayashi, Miki Shimbo, Hyojung Jeon, Takahisa Miyao, Maki Miyauchi, Masaki Shirakawa, Dai Shiba, Nobuaki Yoshida, Masafumi Muratani, Satoru Takahashi, Taishin Akiyama
Hindlimb unloading (HU) of rodents has been used as a ground-based model of spaceflight. In this study, we investigated the detailed impact of 14-day HU on the murine thymus. Thymic mass and cell number were significantly reduced after 14 days of hindlimb unloading, which was accompanied by an increment of plasma corticosterone. Although corticosterone reportedly causes selective apoptosis of CD4+ CD8+ thymocytes (CD4+ CD8+ DPs) in mice treated with short-term HU, the reduction of thymocyte cellularity after the 14-day HU was not selective for CD4+ CD8+ DPs...
May 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29751003/special-at-rich-binding1-protein-satb1-in-malignant-t-cells
#10
Simon Fredholm, Andreas Willerslev-Olsen, Özcan Met, Linda Kubat, Maria Gluud, Sarah L Mathiasen, Christina Friese, Edda Blümel, David L Petersen, Tengpeng Hu, Claudia Nastasi, Lise M Lindahl, Terkild B Buus, Thorbjørn Krejsgaard, Mariusz A Wasik, Katharina L Kopp, Sergei B Koralov, Jenny L Persson, Charlotte M Bonefeld, Carsten Geisler, Anders Woetmann, Lars Iversen, Jurgen C Becker, Niels Odum
Deficient expression of Suppressor Special AT-rich Binding-1 (SATB1) hampers thymocyte development and results in inept T cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides (MF), the most frequent variant of cutaneous T cell lymphoma (CTCL). Here we report on a disease-stage-associated decrease of SATB1 expression and an inverse expression of STAT5 and SATB1 in situ. Importantly, STAT5 inhibited SATB1 expression through induction of miR-155. Decreased SATB1 expression triggered enhanced expression of IL-5 and IL-9 (but not IL-6 and IL-32) whereas increased SATB1 expression had the opposite effect indicating that the mir-155 target SATB1 is a repressor of IL-5 and IL-9 in malignant T cells...
May 8, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29749372/the-thioredoxin-1-system-is-essential-for-fueling-dna-synthesis-during-t-cell-metabolic-reprogramming-and-proliferation
#11
Jonathan Muri, Sebastian Heer, Mai Matsushita, Lea Pohlmeier, Luigi Tortola, Tobias Fuhrer, Marcus Conrad, Nicola Zamboni, Jan Kisielow, Manfred Kopf
The thioredoxin-1 (Trx1) system is an important contributor to cellular redox balance and is a sensor of energy and glucose metabolism. Here we show critical c-Myc-dependent activation of the Trx1 system during thymocyte and peripheral T-cell proliferation, but repression during T-cell quiescence. Deletion of thioredoxin reductase-1 (Txnrd1) prevents expansion the CD4- CD8- thymocyte population, whereas Txnrd1 deletion in CD4+ CD8+ thymocytes does not affect further maturation and peripheral homeostasis of αβT cells...
May 10, 2018: Nature Communications
https://www.readbyqxmd.com/read/29745014/posttransplant-cyclophosphamide-for-haploidentical-stem-cell-transplantation-in-children-with-wiskott-aldrich-syndrome
#12
Yan Yue, Xiaodong Shi, Zeliang Song, Jiayue Qin, Junhui Li, Shunqiao Feng, Rong Liu
BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is the curative treatment for Wiskott-Aldrich syndrome (WAS). However, it is difficult to find a matched donor for patients. Therefore, haploidentical donors should be considered for patients lacking a suitable donor. Our pilot study evaluated whether HSCT with posttransplantation cyclophosphamide (PTCy) is an effective treatment for WAS. METHODS: Haploidentical family donors were selected as donor sources for a total of five patients without a suitable donor between March 2015 and March 2017...
May 10, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29740426/multipotent-adult-progenitor-cells-suppress-t-cell-activation-in-in-vivo-models-of-homeostatic-proliferation-in-a-prostaglandin-e2-dependent-manner
#13
Fiona Carty, Jennifer M Corbett, João Paulo M C M Cunha, James L Reading, Timothy I M Tree, Anthony E Ting, Samantha R Stubblefield, Karen English
Lymphodepletion strategies are used in the setting of transplantation (including bone marrow, hematopoietic cell, and solid organ) to create space or to prevent allograft rejection and graft versus host disease. Following lymphodepletion, there is an excess of IL-7 available, and T cells that escape depletion respond to this cytokine undergoing accelerated proliferation. Moreover, this environment promotes the skew of T cells to a Th1 pro-inflammatory phenotype. Existing immunosuppressive regimens fail to control this homeostatic proliferative (HP) response, and thus the development of strategies to successfully control HP while sparing T cell reconstitution (providing a functioning immune system) represents a significant unmet need in patients requiring lymphodepletion...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29738764/recirculating-th2-cells-induce-severe-thymic-dysfunction-via-il-4-stat6-signaling-pathway
#14
Hui Shen, Chen Yin, Ya-Nan Gao, Xiao-Yan Pei, Xiu-Yuan Sun, Qing Ge, Wei Wang, Yu Zhang
Thymic involution happened early in life, but a certain ratio of activated CD4+ T cells will persistently recirculate into the thymus from the periphery and it have been suggested to be able to inhibit the development of embryonic thymocytes. Our present study was aimed to elucidate the specific mechanism how activated CD4+ T cells could influence upon developing thymocytes by using fetal thymic organ culture (FTOC) and kidney capsule transplantation. Our results demonstrated that Th2 cells were found to play a fundamental role in the inhibition of embryonic thymocyte development since a very low concentration of Th2 cells could obviously reduce the total number of thymocytes...
May 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29735644/invariant-nkt-cells-and-control-of-the-thymus-medulla
#15
REVIEW
Andrea J White, Beth Lucas, William E Jenkinson, Graham Anderson
Most αβ T cells that form in the thymus are generated during mainstream conventional thymocyte development and involve the generation and selection of a diverse αβ TCR repertoire that recognizes self-peptide/MHC complexes. Additionally, the thymus also supports the production of T cell subsets that express αβ TCRs but display unique developmental and functional features distinct from conventional αβ T cells. These include multiple lineages of CD1d-restricted invariant NKT (iNKT) cells that express an invariant αβ TCR, branch off from mainstream thymocytes at the CD4+ CD8+ stage, and are potent producers of polarizing cytokines...
May 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29731924/the-spectrum-of-histopathological-changes-in-the-renal-allograft-a-12-months-protocol-biopsy-study
#16
Galina Severova-Andreevska, Ladislava Grcevska, Gordana Petrushevska, Koco Cakalaroski, Aleksandar Sikole, Olivera Stojceva-Taneva, Ilina Danilovska, Ninoslav Ivanovski
INTRODUCTION: Renal transplantation became a routine and successful medical treatment for Chronic Kidney Disease in the last 30 years all over the world. Introduction of Luminex based Single Antigen Beads (SAB) and recent BANFF consensus of histopathological phenotypes of different forms of rejection enables more precise diagnosis and changes the therapeutic approach. The graft biopsies, protocol or cause, indicated, remain a golden diagnostic tool for clinical follow up of kidney transplant recipients (KTR)...
April 15, 2018: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/29731087/seven-years-of-experiences-of-preclinical-experiments-of-xeno-heart-transplantation-of-pig-to-non-human-primate-cynomolgus-monkey
#17
S J Lee, J S Kim, H K Chee, I J Yun, K S Park, H S Yang, J H Park
BACKGROUND: The absolute shortage of donors compared with patients requiring transplantation is currently an unsolved problem, and the only possible solution may be xenotransplantation. To establish a successful clinical trial, a preclinical study using nonhuman primates is essential. Starting in November 2011, our team initiated heterotopic abdominal heart xenotransplantation, the first in the Republic of Korea. We present here the initial 7-year results. METHODS: A total of 22 xenotransplantation procedures have been performed since 2011...
May 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29730559/mln3126-an-antagonist-of-the-chemokine-receptor-ccr9-ameliorates-inflammation-in-a-t-cell-mediated-mouse-colitis-model
#18
Keiko Igaki, Yusaku Komoike, Yoshiki Nakamura, Takeshi Watanabe, Masashi Yamasaki, Paul Fleming, Lili Yang, Dulce Soler, Eric Fedyk, Noboru Tsuchimori
C-C chemokine receptor 9 (CCR9) is the homing receptor for C-C motif chemokine ligand 25 (CCL25), and contributes to the maintenance of mucosal immunity and pathogenesis of inflammatory bowel disease (IBD) through the recruitment of T cells into the gut mucosa. Recent reports suggest that the interaction of CCR9 and CCL25 in the large intestine correlate with disease severity of colonic IBD. MLN3126 is an orally available small molecular compound with potent and selective CCR9 antagonist activity. MLN3126 inhibited CCL25-induced calcium mobilization in human CCR9 transfected cells and CCL25-induced chemotaxis of mouse primary thymocytes in a dose-dependent manner...
May 3, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29726044/%C3%AE-%C3%AE-t-cell-receptors-with-a-central-cdr3-cysteine-are-enriched-in-cd8%C3%AE-%C3%AE-intraepithelial-lymphocytes-and-their-thymic-precursors
#19
Rushika C Wirasinha, Mandeep Singh, Stuart K Archer, Anna Chan, Paul F Harrison, Christopher C Goodnow, Stephen R Daley
The thymus plays a crucial role in immune tolerance by exposing developing T cells (thymocytes) to a myriad of self-antigens. Strong T-cell receptor (TCR) engagement induces tolerance in self-reactive thymocytes by stimulating apoptosis or selection into specialized T-cell lineages, including intestinal TCRαβ+ CD8αα+ intraepithelial lymphocytes (IEL). TCR-intrinsic amino acid motifs that can be used to predict whether a TCR will be strongly self-reactive remain elusive. Here, a novel TCR sequence alignment approach revealed that T-cell lineages in C57BL/6 mice had divergent usage of cysteine within two positions of the amino acid at the apex of the complementarity-determining region 3 (CDR3) of the TCRα or TCRβ chain...
May 3, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29714032/alemtuzumab-versus-anti-thymocyte-globulin-in-patients-transplanted-from-an-unrelated-donor-after-a-reduced-intensity-conditioning
#20
Marie Robin, Kavita Raj, Sylvie Chevret, Jordan Gauthier, Hugues de Lavallade, David Michonneau, Donal McLornan, Régis Peffault de Latour, Victoria Potter, Austin Kulasekararaj, Flore Sicre de Fontbrune, Antonio Pagliuca, Ibrahim Yakoub-Agha, Gérard Socié, Ghulam J Mufti
OBJECTIVE: Relapse and graft-versus-host disease are still the main complications after allogeneic hematopoietic stem cell transplantation, especially in the setting of reduced intensity regimen (RIC) and unrelated donor. We compared here anti-thymocyte globulin (ATG) or alemtuzumab as GVHD prophylaxis in patients with myeloid disease transplanted after RIC and from an unrelated donor. METHOD: ATG- and alemtuzumab -patients have been matched by age, gender, HLA matching, comorbidities and cytogenetics risk (119 patients in each group)...
April 30, 2018: European Journal of Haematology
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