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Frank Portillo, William R Branch, Werner Conradie, Mark-Oliver Rödel, Johannes Penner, Michael F Barej, Chifundera Kusamba, Wandege M Muninga, Mwenebatu M Aristote, Aaron M Bauer, Jean-François Trape, Zoltán T Nagy, Piero Carlino, Olivier S G Pauwels, Michele Menegon, Marius Burger, Tomáš Mazuch, Kate Jackson, Daniel F Hughes, Mathias Behangana, Eli Greenbaum
Members of the snake subfamily Aparallactinae occur in various habitats throughout sub-Saharan Africa. The monophyly of aparallactine snakes is well established, but relationships within the subfamily are poorly known. We sampled 158 individuals from six of eight aparallactine genera in sub-Saharan Africa. We employed concatenated gene-tree analyses, divergence dating approaches, and ancestral-area reconstructions to infer phylogenies and biogeographic patterns with a multi-locus data set consisting of three mitochondrial (16S, cyt b, and ND4) and two nuclear genes (c-mos and RAG1)...
March 15, 2018: Molecular Phylogenetics and Evolution
Patrick Belikan, Ulrike Bühler, Christina Wolf, Gautam K Pramanik, René Gollan, Frauke Zipp, Volker Siffrin
Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the CNS. Myelin-specific CD4+ Th lymphocytes are known to play a major role in both MS and its animal model experimental autoimmune encephalomyelitis (EAE). CCR7 is a critical element for immune cell trafficking and recirculation, that is, lymph node homing, under homeostatic conditions; blocking CCR7+ central memory cells from egress of lymph nodes is a therapeutic approach in MS. To define the effect of CD4+ T cell-specific constitutive deletion of CCR7 in the priming and effector phase in EAE, we used an active EAE approach in T cell reconstituted Rag1-/- mice, as well as adoptive transfer EAE, in which mice received in vitro-primed CCR7-/- or CCR7+/+ myelin Ag TCR-transgenic 2d2 Th17 cells...
March 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Rodrigo J da Graça, Thomaz M C Fabrin, Luciano S Gasques, Sônia M A P Prioli, Juan A Balbuena, Alberto J Prioli, Ricardo M Takemoto
Cophylogenetic studies aim at testing specific hypotheses to understand the nature of coevolving associations between sets of organisms, such as host and parasites. Monogeneans and their hosts provide and interesting platform for these studies due to their high host specificity. In this context, the objective of the present study was to establish whether the relationship between Anacanthorus spp. with their hosts from the upper Paraná River and its tributaries can be explained by means of cospeciation processes...
2018: PloS One
Justine M Abais-Battad, Hayley Lund, Daniel J Fehrenbach, John Henry Dasinger, David L Mattson
The current study, performed in Dahl Salt-Sensitive (SS) and SS-Rag1-/- rats lacking T- and B- lymphocytes, tested the hypothesis that immune cells amplify salt-sensitive hypertension and kidney damage in response to a high protein diet. After weaning, SS and SS-Rag1-/- rats were placed on an isocaloric, 0.4% NaCl diet containing normal (18%) or high (30%) protein. At 9 weeks of age, rats were switched to a 4.0% NaCl diet containing the same amount of dietary protein and maintained on the high salt diet for 3 weeks...
March 14, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Katarina Stanko, Christina Iwert, Christine Appelt, Katrin Vogt, Julia Schumann, Franziska Janina Strunk, Stefanie Ahrlich, Stephan Schlickeiser, Chiara Romagnani, Karsten Jürchott, Christian Meisel, Gerald Willimsky, Anja A Kühl, Birgit Sawitzki
Recent findings demonstrated proinflammatory functions of interleukin (IL)-9-producing T helper type (Th) 9 cells in the pathogenesis of intestinal bowel diseases (IBDs). However, also antiinflammatory properties have been ascribed to Th9 cells, pointing to a functional heterogeneity. To dissect the specific expression pattern and, especially, diversity of murine antigen-specific Th9 cells, we applied single cell transcription profiling. Th9 cells displayed reduced expression of typical activation markers, such as Cd40 ligand and Cd96 , whereas expression of Cd25 and Cd83 was increased compared with other Th subsets...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
G Yu, W J Wang, D R Liu, Z F Tao, X Y Hui, J Hou, J Q Sun, X C Wang
Objective: To investigate the clinical characteristics of 8 immunodeficiency cases caused by human recombination activating gene 1 (RAG1) mutations, and to explore the relationship among genotypes, clinical manifestations and immunophenotypes. Methods: Clinical data were collected and analyzed from patients with RAG1 mutations who visited the Department of Clinical Immunology, Children's Hospital of Fudan University between October 2013 and June 2017. The data included clinical manifestations, immunophenotypes and genotypes...
March 2, 2018: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
Maria Moysidou, Sevasti Karaliota, Elisavet Kodela, Maria Salagianni, Yassemi Koutmani, Antonia Katsouda, Konstantia Kodella, Panagiotis Tsakanikas, Styliani Ourailidou, Evangelos Andreakos, Nikolaos Kostomitsopoulos, Dimitris Skokos, Antonios Chatzigeorgiou, Kyoung-Jin Chung, Stefan Bornstein, Mark W Sleeman, Triantafyllos Chavakis, Katia P Karalis
Although accumulation of lymphocytes in the white adipose tissue (WAT) in obesity is linked to insulin resistance, it remains unclear whether lymphocytes also participate in the regulation of energy homeostasis in the WAT. Here, we demonstrate enhanced energy dissipation in Rag1-/- mice, increased catecholaminergic input to subcutaneous WAT, and significant beige adipogenesis. Adoptive transfer experiments demonstrated that CD8+ T cell deficiency accounts for the enhanced beige adipogenesis in Rag1-/- mice...
March 8, 2018: JCI Insight
Brinda Bhatt, Peng Zeng, Huabin Zhu, Sathish Sivaprakasam, Siyi Li, Haiyan Xiao, Lixin Dong, Pamela Shiao, Ravindra Kolhe, Nikhil Patel, Honglin Li, Daniel Levy-Bercowski, Vadivel Ganapathy, Nagendra Singh
A set of coordinated interactions between gut microbiota and the immune cells surveilling the intestine play a key role in shaping local immune responses and intestinal health. Gpr109a is a G protein-coupled receptor expressed at a very high level on innate immune cells and previously shown to play a key role in the induction of colonic regulatory T cells. In this study, we show that Gpr109a-/- Rag1-/- mice exhibit spontaneous rectal prolapse and colonic inflammation, characterized by the presence of an elevated number of IL-17-producing Rorγt+ innate lymphoid cells (ILCs; ILC3)...
March 7, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Zhi-Bin Zhao, Jie Long, Yang-Yang Zhao, Jing-Bo Yang, Wei Jiang, Qing-Zhi Liu, Kai Yan, Liang Li, Yu-Cai Wang, Zhe-Xiong Lian
Sorafenib is a kinase inhibitor approved for the treatment of primary kidney cancer, advanced primary liver cancer, and radioactive iodine resistant advanced thyroid carcinoma. However, sorafenib usually causes serious side effects, which limit its antitumor effect. Nanoparticle based drug delivery systems have been widely used to enhance the therapeutic effects and reduce the side effects of this drug by the enhanced permeability and retention (EPR) effect. Herein, to improve the therapeutic effect of sorafenib, we developed poly(ethylene glycol)-b-poly(lactic acid-co-glycolic acid) (PEG-PLGA) based nanoparticles by a dialysis method for sorafenib encapsulation...
March 7, 2018: Biomaterials Science
Rosane Silva-Santos, Jorge L Ramirez, Pedro M Galetti, Patrícia D Freitas
The megadiversity of the neotropical ichthyofauna has been associated to recent diversification processes, reflecting in subtle or lacking morphological differentiation between species, challenging the classical taxonomic identification. Leporinus friderici occurs in several river basins of South America, and its nominal taxonomic validity has been questioned. Its wide distribution within the Brazilian Shield suggests that this species could be genetically structured among the hydrographic basins, despite a sharp morphological similarity...
2018: Frontiers in Genetics
Lindsey A Muir, Samadhi Kiridena, Cameron Griffin, Jennifer B DelProposto, Lynn Geletka, Gabriel Martinez-Santibañez, Brian F Zamarron, Hannah Lucas, Kanakadurga Singer, Robert W O' Rourke, Carey N Lumeng
Obesity-related changes in adipose tissue leukocytes, in particular adipose tissue macrophages (ATMs) and dendritic cells (ATDCs), are implicated in metabolic inflammation, insulin resistance, and altered regulation of adipocyte function. We evaluated stromal cell and white adipose tissue (WAT) expansion dynamics with high fat diet (HFD) feeding for 3-56 days, quantifying ATMs, ATDCs, endothelial cells (ECs), and preadipocytes (PAs) in visceral epididymal WAT and subcutaneous inguinal WAT. To better understand mechanisms of the early response to obesity, we evaluated ATM proliferation and lipid accumulation...
March 1, 2018: Journal of Leukocyte Biology
Michelle Ma, Jamie L Redes, Caroline M Percopo, Kirk M Druey, Helene F Rosenberg
BACKGROUND: Eosinophils in the nasal mucosa are an elemental feature of allergic rhinitis. OBJECTIVE: Our objective was to explore eosinophilic inflammation and its impact on respiratory virus infection at the nasal mucosa. METHODS: Inflammation in the nasal mucosae of mice was evaluated in response to repetitive stimulation with strict intranasal volumes of a filtrate of Alternaria alternata. Mice were then challenged with influenza virus...
February 23, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Mingfeng Zhang, Jeremy J Racine, Qing Lin, Yuqing Liu, Shanshan Tang, Qi Qin, Tong Qi, Arthur D Riggs, Defu Zeng
Autoimmune type 1 diabetes (T1D) and other autoimmune diseases are associated with particular MHC haplotypes and expansion of autoreactive T cells. Induction of MHC-mismatched but not -matched mixed chimerism by hematopoietic cell transplantation effectively reverses autoimmunity in diabetic nonobese diabetic (NOD) mice, even those with established diabetes. As expected, MHC-mismatched mixed chimerism mediates deletion in the thymus of host-type autoreactive T cells that have T-cell receptor (TCR) recognizing (cross-reacting with) donor-type antigen presenting cells (APCs), which have come to reside in the thymus...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Michihito Kono, Nobuya Yoshida, Kayaho Maeda, George C Tsokos
Glutaminolysis is a well-known source of energy for effector T cells but its contribution to each T cell subset and the mechanisms which are responsible for the control of involved metabolic enzymes are not fully understood. We report that Th17 but not Th1, Th2, or Treg cell induction in vitro depends on glutaminolysis and the up-regulation of glutaminase 1 (Gls1), the first enzyme in the glutaminolysis pathway. Both pharmacological and siRNA-based selective inhibition of Gls1 reduced in vitro Th17 differentiation and reduced the CD3/TCR-mediated increase of the mammalian target of rapamycin complex 1 activity...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Elisavet Kodela, Maria Moysidou, Sevasti Karaliota, Yassemi Koutmani, Panagiotis Tsakanikas, Konstantia Kodella, Eleni A Karavia, Kyriakos E Kypreos, Nikolaos Kostomitsopoulos, Katia P Karalis
Obesity is characterized as a chronic, low-grade inflammatory disease owing to the infiltration of the adipose tissue by macrophages. Although the role of macrophages in this process is well established, the role of lymphocytes in the development of obesity and metabolism remains less well defined. In the current study, we fed WT and Rag1-/- male mice, of C57BL/6J and BALB/c backgrounds, high-fat diet (HFD) or normal diet for 15 wk. Compared with WT mice, Rag1-/- mice of either of the examined strains were found less prone to insulin resistance after HFD, had higher metabolic rates, and used lipids more efficiently, as shown by the increased expression of genes related to fatty acid oxidation in epidydimal white adipose tissue...
February 1, 2018: Comparative Medicine
Marina Walker, Mariana L Lyra, Célio F B Haddad
The genus Fritziana (Anura: Hemiphractidae) comprises six described species (F. goeldii, F. ohausi, F. fissilis, F. ulei, F. tonimi, and F. izecksohni) that are endemic to the Brazilian Atlantic Forest. Although the genus has been the subject of studies dealing with its taxonomy, phylogeny, and systematics, there is considerable evidence for cryptic diversity hidden among the species. The present study aims to understand the genetic diversity and phylogenetic relationships among the species of Fritziana, as well as the relationships among populations within species...
February 13, 2018: Molecular Phylogenetics and Evolution
Qingyu Cheng, Laleh Khodadadi, Adriano Taddeo, Jens Klotsche, Bimba F Hoyer, Andreas Radbruch, Falk Hiepe
Antibody-secreting cells (ASCs), including short-lived plasmablasts and long-lived memory plasma cells (LLPCs), contribute to autoimmune pathology. ASCs, particularly LLPCs, refractory to conventional immunosuppressive drugs pose a major therapeutic challenge. Since stromal cells expressing C-X-C motif chemokine-12 (CXCL12) organize survival niches for LLPCs in the bone marrow, we investigated the effects of CXCL12 and its ligand CXCR4 on ASCs in lupus mice (NZB/W). Fewer adoptively transferred splenic ASCs were retrieved from the bone marrow of recipient immunodeficient Rag1-/- mice when the ASCs were pre-treated with the CXCR4 blocker AMD3100...
February 10, 2018: European Journal of Immunology
Fanyou Ning, Chong Wang, Suling Niu, Haiyan Xu, Kai Xia, Nan Wang
The Polycomb Repressive Complex 2 (PRC2) component PHD Finger Protein 19 (phf19) gene has been identified to be associated with rheumatoid arthritis (RA) risk. Here we show that Phf19 is highly expressed in murine germinal centers (GCs) and RA patients. To investigate the function of Phf19 in lymphocytes, we generated RAG1-deficient mice reconstituted with Phf19 or control-vector transduced bone marrow (BM) cells. Lymphogenesis in primary lymphoid tissues of Phf19-RM is normal, however, Phf19-RM form enlarged GCs and generate more antibody-secreting cells (ASCs)...
2018: American Journal of Translational Research
Jennifer Brasseit, Cheong K C Kwong Chung, Mario Noti, Daniel Zysset, Nina Hoheisel-Dickgreber, Vera Genitsch, Nadia Corazza, Christoph Mueller
Aberrant interferon gamma (IFNγ) expression is associated with the pathogenesis of numerous autoimmune- and inflammatory disorders, including inflammatory bowel diseases (IBD). However, the requirement of IFNγ for the pathogenesis of chronic intestinal inflammation remains controversial. The aim of this study was thus to investigate the role of IFNγ in experimental mouse models of innate and adaptive immune cell-mediated intestinal inflammation using genetically and microbiota-stabilized hosts. While we find that IFNγ drives acute intestinal inflammation in the anti-CD40 colitis model in an innate lymphoid cell (ILC)-dependent manner, IFNγ secreted by both transferred CD4 T cells and/or cells of the lymphopenic Rag1 -/- recipient mice was dispensable for CD4 T cell-mediated colitis...
2018: Frontiers in Immunology
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
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