journal
MENU ▼
Read by QxMD icon Read
search

Journal of Clinical Investigation

journal
https://www.readbyqxmd.com/read/29782330/a-transgenic-mouse-model-for-hla-b-57-01-linked-abacavir-drug-tolerance-and-reactivity
#1
Marco Cardone, Karla Garcia, Mulualem E Tilahun, Lisa F Boyd, Sintayehu Gebreyohannes, Masahide Yano, Gregory Roderiquez, Adovi D Akue, Leslie Juengst, Elliot Mattson, Suryatheja Ananthula, Kannan Natarajan, Montserrat Puig, David H Margulies, Michael A Norcross
Adverse drug reactions (ADRs) are a major obstacle to drug development, and some of these, including hypersensitivity reactions to the HIV reverse transcriptase inhibitor abacavir (ABC), are associated with HLA alleles, particularly HLA-B*57:01. However, not all HLA-B*57:01+ patients develop ADRs, suggesting that in addition to the HLA genetic risk, other factors may influence the outcome of the response to the drug. To study HLA-linked ADRs in vivo, we generated HLA-B*57:01-Tg mice and show that, although ABC activated Tg mouse CD8+ T cells in vitro in a HLA-B*57:01-dependent manner, the drug was tolerated in vivo...
May 21, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29781815/lymph-node-fibrosis-a-structural-barrier-to-unleashing-effective-vaccine-immunity
#2
Boris Julg, Galit Alter
There is marked variability in vaccine efficacy among global populations. In particular, individuals in low- to middle-income countries have been shown to be less responsive to vaccines than those from developed nations. Several factors, including endemic infections, nutrition, genetics, and gut microbiome composition, have been proposed to underlie discrepancies in vaccine response. In this issue of the JCI, Kityo et al. evaluated response to yellow fever virus vaccine, inflammation, and lymphatic tissue architecture and fibrosis in three cohorts: two from the U...
May 21, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29781814/lymphoid-tissue-fibrosis-is-associated-with-impaired-vaccine-responses
#3
Cissy Kityo, Krystelle Nganou Makamdop, Meghan Rothenberger, Jeffrey G Chipman, Torfi Hoskuldsson, Gregory J Beilman, Bartosz Grzywacz, Peter Mugyenyi, Francis Ssali, Rama S Akondy, Jodi Anderson, Thomas E Schmidt, Thomas Reimann, Samuel P Callisto, Jordan Schoephoerster, Jared Schuster, Proscovia Muloma, Patrick Ssengendo, Eirini Moysi, Constantinos Petrovas, Ray Lanciotti, Lin Zhang, Maria T Arévalo, Benigno Rodriguez, Ted M Ross, Lydie Trautmann, Rafick-Pierre Sekaly, Michael M Lederman, Richard A Koup, Rafi Ahmed, Cavan Reilly, Daniel C Douek, Timothy W Schacker
Vaccine responses vary by geographic location. We have previously described how HIV-associated inflammation leads to fibrosis of secondary lymph nodes (LNs) and T cell depletion. We hypothesized that other infections may cause LN inflammation and fibrosis, in a process similar to that seen in HIV infection, which may lead to T cell depletion and affect vaccine responses. We studied LNs of individuals from Kampala, Uganda, before and after yellow fever vaccination (YFV) and found fibrosis in LNs that was similar to that seen in HIV infection...
May 21, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29781813/the-notch1-cd44-axis-drives-pathogenesis-in-a-t-cell-acute-lymphoblastic-leukemia-model
#4
Marina García-Peydró, Patricia Fuentes, Marta Mosquera, María J García-León, Juan Alcain, Antonio Rodríguez, Purificación García de Miguel, Pablo Menéndez, Kees Weijer, Hergen Spits, David T Scadden, Carlos Cuesta-Mateos, Cecilia Muñoz-Calleja, Francisco Sánchez-Madrid, María L Toribio
NOTCH1 is a prevalent signaling pathway in T cell acute lymphoblastic leukemia (T-ALL), but crucial NOTCH1 downstream signals and target genes contributing to T-ALL pathogenesis cannot be retrospectively analyzed in patients and thus remain ill defined. This information is clinically relevant, as initiating lesions that lead to cell transformation and leukemia-initiating cell (LIC) activity are promising therapeutic targets against the major hurdle of T-ALL relapse. Here, we describe the generation in vivo of a human T cell leukemia that recapitulates T-ALL in patients, which arises de novo in immunodeficient mice reconstituted with human hematopoietic progenitors ectopically expressing active NOTCH1...
May 21, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29781812/pim-2-protein-kinase-negatively-regulates-t-cell-responses-in-transplantation-and-tumor-immunity
#5
Anusara Daenthanasanmak, Yongxia Wu, Supinya Iamsawat, Hung D Nguyen, David Bastian, MengMeng Zhang, M Hanief Sofi, Shilpak Chatterjee, Elizabeth G Hill, Shikhar Mehrotra, Andrew S Kraft, Xue-Zhong Yu
PIM kinase family members play a crucial role in promoting cell survival and proliferation via phosphorylation of their target substrates. In this study, we investigated the role of the PIM kinases with respect to T cell responses in transplantation and tumor immunity. We found that the PIM-2 isoform negatively regulated T cell responses to alloantigen, in contrast to the PIM-1 and PIM-3 isoforms, which acted as positive regulators. T cells deficient in PIM-2 demonstrated increased T cell differentiation toward Th1 subset, proliferation, and migration to target organs after allogeneic bone marrow transplantation, resulting in dramatically accelerated graft-versus-host disease (GVHD) severity...
May 21, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29781811/spleen-derived-classical-monocytes-mediate-lung-ischemia-reperfusion-injury-through-il-1%C3%AE
#6
Hsi-Min Hsiao, Ramiro Fernandez, Satona Tanaka, Wenjun Li, Jessica H Spahn, Stephen Chiu, Mahzad Akbarpour, Daniel Ruiz-Perez, Qiang Wu, Cem Turam, Davide Scozzi, Tsuyoshi Takahashi, Hannah P Luehmann, Varun Puri, G R Scott Budinger, Alexander S Krupnick, Alexander V Misharin, Kory J Lavine, Yongjian Liu, Andrew E Gelman, Ankit Bharat, Daniel Kreisel
Ischemia-reperfusion injury, a form of sterile inflammation, is the leading risk factor for both short-term mortality following pulmonary transplantation and chronic lung allograft dysfunction. While it is well recognized that neutrophils are critical mediators of acute lung injury, processes that guide their entry into pulmonary tissue are not well understood. Here, we found that CCR2+ classical monocytes are necessary and sufficient for mediating extravasation of neutrophils into pulmonary tissue during ischemia-reperfusion injury following hilar clamping or lung transplantation...
May 21, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29781810/active-suppression-rather-than-ignorance-tolerance-to-abacavir-induced-hla-b-57-01-peptide-repertoire-alteration
#7
Elizabeth J Phillips, Simon A Mallal
The discovery of HLA-B*57:01-associated abacavir hypersensitivity is a translational success story that eliminated adverse reactions to abacavir through pretreatment screening and defined a mechanistic model of an altered peptide repertoire. In this issue of the JCI, Cardone et al. have developed an HLA-B*57:01-transgenic mouse model and demonstrated that CD4+ T cells play a key role in mediating tolerance to the dramatically altered endogenous peptide repertoire induced by abacavir and postulate a known mechanism by which CD4+ T cells suppress DC maturation...
May 21, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29771686/spleen-mediates-a-distinct-hematopoietic-progenitor-response-supporting-tumor-promoting-myelopoiesis
#8
Chong Wu, Huiheng Ning, Mingyu Liu, Jie Lin, Shufeng Luo, Wenjie Zhu, Jing Xu, Wen-Chao Wu, Jing Liang, Chun-Kui Shao, Jiaqi Ren, Bin Wei, Jun Cui, Min-Shan Chen, Limin Zheng
Cancer progression is associated with alterations of intra- and extramedullary hematopoiesis to support a systemic tumor-promoting myeloid response. However, the functional specialty, mechanism, and clinical relevance of extramedullary hematopoiesis (EMH) remain unclear. Here we showed that the heightened splenic myelopoiesis in tumor-bearing hosts was not only characterized by the accumulation of myeloid precursors, but also associated with profound functional alterations of splenic early hematopoietic stem/progenitor cells (HSPCs)...
May 17, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29771685/enterotoxigenic-escherichia-coli-blood-group-a-interactions-intensify-diarrheal-severity
#9
Pardeep Kumar, F Matthew Kuhlmann, Subhra Chakroborty, A Louis Bourgeois, Jennifer Foulke-Abel, Brunda Tumala, Tim J Vickers, David A Sack, Barbara DeNearing, Clayton D Harro, W Shea Wright, Jeffrey C Gildersleeve, Matthew A Ciorba, Srikanth Santhanam, Chad K Porter, Ramiro L Gutierrez, Michael G Prouty, Mark S Riddle, Alexander Polino, Alaullah Sheikh, Mark Donowitz, James M Fleckenstein
Enterotoxigenic Escherichia coli (ETEC) infections are highly prevalent in developing countries where clinical presentations range from asymptomatic colonization to severe cholera-like illness. The molecular basis for these varied presentations, that may involve strain-specific virulence features as well as host factors, have not been elucidated. We demonstrate that when challenged with ETEC strain H10407, originally isolated from a case of cholera-like illness, blood group A human volunteers developed severe diarrhea more frequently than individuals from other blood groups...
May 17, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29771684/antibiotic-treatment-induced-secondary-iga-deficiency-enhances-susceptibility-to-pseudomonas-aeruginosa-pneumonia
#10
Oliver H Robak, Markus M Heimesaat, Andrey A Kruglov, Sandra Prepens, Justus Ninnemann, Birgitt Gutbier, Katrin Reppe, Hubertus Hochrein, Mark Suter, Carsten J Kirschning, Veena Marathe, Jan Buer, Mathias W Hornef, Markus Schnare, Pascal Schneider, Martin Witzenrath, Stefan Bereswill, Ulrich Steinhoff, Norbert Suttorp, Leif E Sander, Catherine Chaput, Bastian Opitz
Broad-spectrum antibiotics are widely used in patients on intensive care units (ICU), many of which develop hospital-acquired infections with Pseudomonas aeruginosa. Although preceding antimicrobial therapy is known as a major risk factor for P. aeruginosa-induced pneumonia, the underlying mechanisms remain incompletely understood. Here we demonstrate that depletion of the resident microbiota by broad-spectrum antibiotic treatment inhibited TLR-dependent production of a proliferation inducing ligand (APRIL), resulting in a secondary IgA deficiency in the lung in mice and human ICU patients...
May 17, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29763414/cd93-promotes-integrin-%C3%AE-1-activation-and-fibronectin-fibrillogenesis-during-tumor-angiogenesis
#11
Roberta Lugano, Kalyani Vemuri, Di Yu, Michael Bergqvist, Anja Smits, Magnus Essand, Staffan Johansson, Elisabetta Dejana, Anna Dimberg
Tumor angiogenesis occurs through regulation of genes that orchestrate endothelial sprouting and vessel maturation, including deposition of a vessel-associated extracellular matrix. CD93 is a transmembrane receptor that is up-regulated in tumor vessels in many cancers, including high-grade glioma. Here, we demonstrate that CD93 regulates integrin-β1-signaling and organization of fibronectin fibrillogenesis during tumor vascularization. In endothelial cells and mouse retina, CD93 was found to be expressed in endothelial filopodia and to promote filopodia formation...
May 15, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29757196/leukotriene-receptors-as-potential-therapeutic-targets
#12
Takehiko Yokomizo, Motonao Nakamura, Takao Shimizu
Leukotrienes, a class of arachidonic acid-derived bioactive molecules, are known as mediators of allergic and inflammatory reactions and considered to be important drug targets. Although an inhibitor of leukotriene biosynthesis and antagonists of the cysteinyl leukotriene receptor are clinically used for bronchial asthma and allergic rhinitis, these medications were developed before the molecular identification of leukotriene receptors. Numerous studies using cloned leukotriene receptors and genetically engineered mice have unveiled new pathophysiological roles for leukotrienes...
May 14, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29757195/resolvins-in-inflammation-emergence-of-the-pro-resolving-superfamily-of-mediators
#13
Charles N Serhan, Bruce D Levy
Countless times each day, the acute inflammatory response protects us from invading microbes, injuries, and insults from within, as in surgery-induced tissue injury. These challenges go unnoticed because they are self-limited and naturally resolve without progressing to chronic inflammation. Peripheral blood markers of inflammation are present in many common diseases, including inflammatory bowel disease, cardiovascular disease, neurodegenerative disease, and cancer. While acute inflammation is protective, excessive swarming of neutrophils amplifies collateral tissue damage and inflammation...
May 14, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29757194/the-expanding-constellation-of-immune-checkpoints-a-dnamic-control-by-cd155
#14
Vincenzo Bronte
The clinical benefits that have been achieved for a group of cancer patients with metastatic disease on checkpoint inhibitor therapy have kindled intense interest in understanding tumor-induced escape from T lymphocyte control. Other lymphoid cells also participate in tumor control; in particular, NK cells can limit hematogenous cancer metastasis spread and are also subject to negative regulation by developing cancers. In this issue of the JCI, Li and colleagues define an unanticipated role for the stress-induced protein CD155 in cancer metastasis...
May 14, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29757193/eya3-promotes-breast-tumor-associated-immune-suppression-via-threonine-phosphatase-mediated-pd-l1-upregulation
#15
Rebecca L Vartuli, Hengbo Zhou, Lingdi Zhang, Rani K Powers, Jared Klarquist, Pratyaydipta Rudra, Melanie Y Vincent, Debashis Ghosh, James C Costello, Ross M Kedl, Jill E Slansky, Rui Zhao, Heide L Ford
Eya proteins are critical developmental regulators that are highly expressed in embryogenesis but downregulated after development. Amplification and/or re-expression of Eyas occurs in many tumor types. In breast cancer, Eyas regulate tumor progression by acting as transcriptional cofactors and tyrosine phosphatases. Intriguingly, Eyas harbor a separate threonine (Thr) phosphatase activity, which was previously implicated in innate immunity. Here we describe what we believe to be a novel role for Eya3 in mediating triple-negative breast cancer-associated immune suppression...
May 14, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29757192/cd155-loss-enhances-tumor-suppression-via-combined-host-and-tumor-intrinsic-mechanisms
#16
Xian-Yang Li, Indrajit Das, Ailin Lepletier, Venkateswar Addala, Tobias Bald, Kimberley Stannard, Deborah Barkauskas, Jing Liu, Amelia Roman Aguilera, Kazuyoshi Takeda, Matthias Braun, Kyohei Nakamura, Sebastien Jacquelin, Steven W Lane, Michele Wl Teng, William C Dougall, Mark J Smyth
Critical immune-suppressive pathways beyond programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) require greater attention. Nectins and nectin-like molecules might be promising targets for immunotherapy, since they play critical roles in cell proliferation and migration and exert immunomodulatory functions in pathophysiological conditions. Here, we show CD155 expression in both malignant cells and tumor-infiltrating myeloid cells in humans and mice. Cd155-/- mice displayed reduced tumor growth and metastasis via DNAM-1 upregulation and enhanced effector function of CD8+ T and NK cells, respectively...
May 14, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29757191/disease-driving-cd4-t-cell-clonotypes-persist-for-decades-in-celiac-disease
#17
Louise F Risnes, Asbjørn Christophersen, Shiva Dahal-Koirala, Ralf S Neumann, Geir K Sandve, Vikas K Sarna, Knut Ea Lundin, Shuo-Wang Qiao, Ludvig M Sollid
Little is known about the repertoire dynamics and persistence of pathogenic T cells in HLA-associated disorders. In celiac disease, a disorder with a strong association with certain HLA-DQ allotypes, presumed pathogenic T cells can be visualized and isolated with HLA-DQ:gluten tetramers, thereby enabling further characterization. Single and bulk populations of HLA-DQ:gluten tetramer-sorted CD4+ T cells were analyzed by high-throughput DNA sequencing of rearranged TCR-α and -β genes. Blood and gut biopsy samples from 21 celiac disease patients, taken at various stages of disease and in intervals of weeks to decades apart, were examined...
May 14, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29757190/reversing-the-curse-on-ppar%C3%AE
#18
Mitchell A Lazar
Thiazolidinediones (TZDs) are the only antidiabetic drugs that reverse insulin resistance. They have been a valuable asset in the treatment of type 2 diabetes, but their side effects have curtailed widespread use in the clinic. In this issue of the JCI, Kraakman and colleagues provide evidence that deacetylation of the nuclear receptor PPARγ improves the therapeutic index of TZDs. These findings should revitalize the quest to employ insulin sensitization as a first-line approach to managing type 2 diabetes...
May 14, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29757189/notch-effector-csl-promotes-squamous-cell-carcinoma-by-repressing-histone-demethylase-kdm6b
#19
Dania Al Labban, Seung-Hee Jo, Paola Ostano, Chiara Saglietti, Massimo Bongiovanni, Renato Panizzon, G Paolo Dotto
Notch 1/2 genes play tumor-suppressing functions in squamous cell carcinoma (SCC), a very common malignancy in skin and internal organs. In contrast with Notch, we show that the transcription factor CSL (also known as RBP-Jκ), a key effector of canonical Notch signaling endowed with intrinsic transcription-repressive functions, plays a tumor-promoting function in SCC development. Expression of this gene decreased in upper epidermal layers and human keratinocytes (HKCs) undergoing differentiation, while it increased in premalignant and malignant SCC lesions from skin, head/neck, and lung...
May 14, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29757188/microrna-210-overexpression-promotes-psoriasis-like-inflammation-by-inducing-th1-and-th17-cell-differentiation
#20
Ruifang Wu, Jinrong Zeng, Jin Yuan, Xinjie Deng, Yi Huang, Lina Chen, Peng Zhang, Huan Feng, Zixin Liu, Zijun Wang, Xiaofei Gao, Haijing Wu, Honglin Wang, Yuwen Su, Ming Zhao, Qianjin Lu
Immune imbalance of T lymphocyte subsets is a hallmark of psoriasis, but the molecular mechanisms underlying this aspect of psoriasis pathology are poorly understood. Here, we report that microRNA-210 (miR-210), a miR that is highly expressed in both psoriasis patients and mouse models, induces helper T (Th) 17 and Th1 cell differentiation but inhibits Th2 differentiation through repressing STAT6 and LYN expression, contributing to several aspects of the immune imbalance in psoriasis. Both miR-210 ablation in mice and inhibition of miR-210 by intradermal injection of antagomir-210 blocked the immune imbalance and the development of psoriasis-like inflammation in an imiquimod-induced or IL-23-induced psoriasis-like mouse model...
May 14, 2018: Journal of Clinical Investigation
journal
journal
27305
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"