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Mariona Camps-Bossacoma, Francisco J Pérez-Cano, Àngels Franch, Margarida Castell
Background: A 10% cocoa-enriched diet influences immune system functionality including the prevention of the antibody response and the induction of lower immunoglobulin (Ig) concentrations. However, neither cocoa polyphenols nor cocoa fiber can totally explain these immunoregulatory properties. Objectives: This study aimed to establish the influence of cocoa theobromine in systemic and intestinal Ig concentrations and to determine the effect of cocoa or theobromine feeding on lymphoid tissue lymphocyte composition...
March 1, 2018: Journal of Nutrition
Christelle Retière, Catherine Willem, Thierry Guillaume, Henri Vié, Laetitia Gautreau-Rolland, Emmanuel Scotet, Xavier Saulquin, Katia Gagne, Marie C Béné, Berthe-Marie Imbert, Beatrice Clemenceau, Pierre Peterlin, Alice Garnier, Patrice Chevallier
We have compared prospectively the outcome and immune reconstitution of patients receiving either post-transplant cyclophosphamide (PTCY) ( n = 30) or anti-thymocyte globulin ATG ( n = 15) as Graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell (PBSC) transplantation (allo-SCT). The outcome and immune reconstitution of patients receiving either of these two regimens were compared prospectively. This study allowed also to investigate the impact of PTCY between haplo-identical vs matched donors and of clofarabine as part of the RIC regimen...
February 20, 2018: Oncotarget
Annalisa Ruggeri, Myriam Labopin, Andrea Bacigalupo, Boris Afanasyev, Jan J Cornelissen, Ahmet Elmaagacli, Maija Itälä-Remes, Didier Blaise, Ellen Meijer, Yener Koc, Noel Milpied, Harry C Schouten, Nicolaus Kroeger, Mohamad Mohty, Arnon Nagler
BACKGROUND: Experience using post-transplant cyclophosphamide (PT-Cy) as graft-versus-host disease (GVHD) prophylaxis in allogeneic stem cell transplantation (HSCT) from matched sibling donors (MSD) or unrelated donors (UD) is limited and with controversial results. The study aim was to evaluate PT-Cy as GVHD prophylaxis post-HSCT from MSD and UD transplants. We analyzed 423 patients with acute leukemia who received PT-Cy alone or in combination with other immunosuppressive (IS) drugs as GVHD prophylaxis...
March 15, 2018: Journal of Hematology & Oncology
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
Alexandros Briasoulis, Chakradhari Inampudi, Mohan Pala, Rabea Asleh, Paulino Alvarez, Jay Bhama
Approximately 50% of heart transplant programs currently employ a strategy of induction therapy (IT) with either interleukin-2 receptor antagonists (IL2RA) or polyclonal anti-thymocyte antibodies (ATG) during the early postoperative period. However, the overall utility of such therapy is uncertain and data comparing induction protocols are limited. The authors searched PubMed, the Cochrane Central Register of Controlled Trials, and through January 2018 for randomized controlled trials (RCTs) or observational controlled studies of IT vs no IT and IL2RA vs ATG...
March 13, 2018: Heart Failure Reviews
Hisashi Wada, Nighat Yasmin, Kiyokazu Kakugawa, Michiko Ohno-Oishi, Sebastian Nieke, Chizuko Miyamoto, Sawako Muroi, Ichiro Taniuchi
During differentiation of CD4+ CD8+ double-positive (DP) thymocytes into the CD4- CD8+ single-positive (CD8SP) thymocytes committed to the cytotoxic T cell lineage, Cd8a transcription is temporally terminated after positive selection and is subsequently reinitiated, a process known as coreceptor reversal. Despite the identification of a transcriptional enhancer in the Cd8a gene that directs reporter transgene expression specifically in CD8SP thymocytes, the molecular mechanisms controlling reactivation of the Cd8a gene are not fully understood...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Ming-Wei Chien, Shin-Huei Fu, Chao-Yuan Hsu, Yu-Wen Liu, Huey-Kang Sytwu
Glycosylation is a ubiquitous posttranslational modification of proteins that occurs in the endoplasmic reticulum/Golgi. N -glycans and mucin-type O -glycans are achieved via a series of glycohydrolase- and glycosyltransferase-mediated reactions. Glycosylation modulates immune responses by regulating thymocyte development and T helper cell differentiation. Autoimmune diseases result from an abnormal immune response by self-antigens and subsequently lead to the destruction of the target tissues. The modification of N -glycans has been studied in several animal models of T-cell-mediated autoimmune diseases...
March 8, 2018: International Journal of Molecular Sciences
Victoria Gröger, Holger Cynis
Human endogenous retroviruses (HERVs) are remnants of retroviral germ line infections of human ancestors and make up ~8% of the human genome. Under physiological conditions, these elements are frequently inactive or non-functional due to deactivating mutations and epigenetic control. However, they can be reactivated under certain pathological conditions and produce viral transcripts and proteins. Several disorders, like multiple sclerosis or amyotrophic lateral sclerosis are associated with increased HERV expression...
2018: Frontiers in Microbiology
Jingru Sun, Shengguo Yi, Lei Qiu, Wenjing Fu, Anqi Wang, Fengjie Liu, Lin Wang, Tingting Wang, Hao Chen, Lei Wang, Marshall E Kadin, Ping Tu, Yang Wang
Cutaneous CD30+ lymphoproliferative disorder (CD30+LPDs), including lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large-cell lymphoma (PCALCL), comprises the second most common group of cutaneous T cell lymphoma. Previously, we reported that special AT-rich sequence-binding protein1 (SATB1), a thymocyte specific chromatin organizer, was over-expressed and promoted malignant T-cell proliferation in a portion of CD30+LPDs. Here, we investigated the expression pattern of SATB1 in CD30+LPDs with a large cohort of patient samples, and examined the potential of SATB1 as a molecular marker to classify CD30+LPDs with differential clinicopathological behaviors...
March 3, 2018: Journal of Investigative Dermatology
Xijun Ou, Jianxin Huo, Yuhan Huang, Yan-Feng Li, Shengli Xu, Kong-Peng Lam
Invariant natural killer T (iNKT) cells develop from CD4+ CD8+ double-positive (DP) thymocytes and express an invariant Vα 14-Jα 18 T-cell receptor (TCR) α-chain. Generation of these cells requires the prolonged survival of DP thymocytes to allow for Vα 14-Jα 18 gene rearrangements and strong TCR signaling to induce the expression of the iNKT lineage-specific transcription factor PLZF. Here, we report that the transcription factor Yin Yang 1 (YY1) is essential for iNKT cell formation. Thymocytes lacking YY1 displayed a block in iNKT cell development at the earliest progenitor stage...
March 2, 2018: Cellular & Molecular Immunology
Andrea Bacigalupo, Rosi Oneto, Hubert Schrezenmeier, Britta Hochsmann, Carlo Dufour, Seiji Kojima, Xiaofan Zhu, Xiaojuan Chen, Surapol Issaragrisil, Suporn Chuncharunee, Dae Chul Jeong, Sabrina Giammarco, Maria Teresa Van Lint, Yizhou Zheng, Carlos Vallejo
The aim of this study was to assess the outcome of patients with aplastic anemia (AA), receiving rabbit anti-thymocyte globulin (Thymoglobulin, SANOFI) and cyclosporin, as first line treatment. Eligible were 955 patients with AA, treated first line with Thymoglobulin, between 2001 and 2008 (n=492), or between 2009-2012 (n=463). The median age of the patients was 21 years (range 1-84). Mortality within 90 days was 5.7% and 2.4%, respectively in the two time periods (p=0.007).The actuarial 10 year survival for the entire population was 70%; transplant free survival was 64%...
March 2, 2018: American Journal of Hematology
Kieran D James, William E Jenkinson, Graham Anderson
T-cells bearing the αβTCR play a vital role in defending the host against foreign pathogens and malignant transformation of self. Importantly, T-cells are required to remain tolerant to the host's own cells and tissues in order to prevent self-reactive responses that can lead to autoimmune disease. T-cells achieve the capacity for self/nonself discrimination by undergoing a highly selective and rigorous developmental program during their maturation in the thymus. This organ is unique in its ability to support a program of T-cell development that ensures the establishment of a functionally diverse αβTCR repertoire within the peripheral T-cell pool...
February 27, 2018: Journal of Leukocyte Biology
Roberto Perniola
About two decades ago, cloning of the autoimmune regulator ( AIRE ) gene materialized one of the most important actors on the scene of self-tolerance. Thymic transcription of genes encoding tissue-specific antigens (ts-ags) is activated by AIRE protein and embodies the essence of thymic self-representation. Pathogenic AIRE variants cause the autoimmune polyglandular syndrome type 1, which is a rare and complex disease that is gaining attention in research on autoimmunity. The animal models of disease, although not identically reproducing the human picture, supply fundamental information on mechanisms and extent of AIRE action: thanks to its multidomain structure, AIRE localizes to chromatin enclosing the target genes, binds to histones, and offers an anchorage to multimolecular complexes involved in initiation and post-initiation events of gene transcription...
2018: Frontiers in Immunology
Shamik Majumdar, Vishwas Mishra, Somesh Nandi, Mudabir Abdullah, Anaxee Barman, Abinaya Raghavan, Dipankar Nandi, Sandhya S Visweswariah
Non-typhoidal Salmonella disease contributes towards significant morbidity and mortality across the world. Host factors including IFN-γ, TNF-α and gut microbiota, significantly influence the outcome of Salmonella pathogenesis. However, the entire repertoire of host protective mechanisms contributing to Salmonella pathogenicity is not completely appreciated. Here, we have investigated the roles of receptor guanylyl cyclase C (GC-C) that is predominantly expressed in the intestine, and regulates intestinal cell proliferation and fluid-ion homeostasis...
February 20, 2018: Infection and Immunity
Shiyun Xiao, Wen Zhang, Nancy R Manley
BACKGROUND: Hematopoietic stem cells (HSCs) derived from birth through adult possess differing differentiation potential for T or B cell fate in the thymus; neonatal bone marrow (BM) cells also have a higher potential for B cell production in BM compared to adult HSCs. We hypothesized that this hematopoietic-intrinsic B potential might also regulate B cell development in the thymus during ontogeny. METHODS: Foxn1lacZ mutant mice are a model in which down regulation of a thymic epithelial cell (TEC) specific transcription factor beginning one week postnatal causes a dramatic reduction of thymocytes production...
2018: PloS One
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
Kiyosumi Ochi, Shigeo Fuji, Kuniko Takano, Kinuko Tajima, Ayumu Ito, Takashi Tanaka, Yoshihiro Inamoto, Saiko Kurosawa, Sung-Won Kim, Arinobu Tojo, Takahiro Fukuda
Polyclonal anti-thymocyte globulins (ATGs) are widely used in allogeneic stem cell transplantation (allo-SCT) for GvHD prophylaxis. ATGs exerted anti-tumor effects in in vitro experiments, but in vivo studies are lacking. We experienced a case of relapsed AML with cells positive for CD7 who underwent haploidentical SCT and unexpectedly achieved a significant reduction of AML cells in the peripheral blood after receiving ATGs before the administration of other drugs in the conditioning regimen. This patient achieved long-term survival after haploidentical SCT...
February 19, 2018: Bone Marrow Transplantation
Nimisha Sulejmani, Shunji Nagai, Mohamed Safwan, Michael D Rizzari, Mohammad Raoufi, Marwan S Abouljoud, Mayur Ramesh
Adenoviruses are double-stranded DNA viruses that typically cause mild self-limiting respiratory, ocular, and gastrointestinal infections. In immunocompromised patients, especially transplant recipients, the infection can be severe, with dissemination and multiorgan failure. In intestinal transplant recipients, the incidence is as high as 57%. To our knowledge, no standardized guidelines or United States Food and Drug Administration-approved medications exist for the treatment of adenovirus disease. We describe two isolated intestinal transplant recipients who developed adenovirus disease (viremia with viral enteritis) that was managed with a new experimental drug, brincidofovir (an oral lipid conjugate prodrug of cidofovir), as salvage therapy...
February 19, 2018: Pharmacotherapy
Paul R Mittelstadt, Matthew D Taves, Jonathan D Ashwell
Glucocorticoid (GC) signaling in thymocytes counters negative selection and promotes the generation of a self-tolerant yet Ag-responsive T cell repertoire. Whereas circulating GC are derived from the adrenals, GC are also synthesized de novo in the thymus. The significance of this local production is unknown. In this study we deleted 11β-hydroxylase, the enzyme that catalyzes the last step of GC biosynthesis, in thymic epithelial cells (TEC) or thymocytes. Like GC receptor-deficient T cells, T cells from mice lacking TEC-derived but not thymocyte-derived GC proliferated poorly to alloantigen, had a reduced antiviral response, and exhibited enhanced negative selection...
February 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Ana Risco, Miguel A Martin-Serrano, Domingo F Barber, Ana Cuenda
p38 mitogen-activated protein kinase (MAPK) signal transduction pathways are essential regulators of the immune response. Particularly, p38γ and p38δ regulate many immune cell functions such as cytokine production, migration, or T cell activation; however, their involvement in immune cell development is largely unknown. Here, we analysed the role of p38 MAPK isoforms p38γ and p38δ in T cell differentiation in the thymus and in lymph nodes, using mice deficient in p38γ, p38δ, or in both. We found that the T cell differentiation program in the thymus was affected at different stages in p38γ-, p38δ-, and p38γ/δ-deficient mice, and also peripheral T cell homaeostasis was compromised...
2018: Frontiers in Immunology
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