journal
https://read.qxmd.com/read/37733279/maternal-diet-during-early-gestation-influences-postnatal-taste-activity-dependent-pruning-by-microglia
#1
JOURNAL ARTICLE
Chengsan Sun, Shuqiu Zheng, Justin S A Perry, Geoffrey T Norris, Mei Cheng, Fanzhen Kong, Rolf Skyberg, Jianhua Cang, Alev Erisir, Jonathan Kipnis, David L Hill
A key process in central sensory circuit development involves activity-dependent pruning of exuberant terminals. Here, we studied gustatory terminal field maturation in the postnatal mouse nucleus of the solitary tract (NST) during normal development and in mice where their mothers were fed a low NaCl diet for a limited period soon after conception. Pruning of terminal fields of gustatory nerves in controls involved the complement system and is likely driven by NaCl-elicited taste activity. In contrast, offspring of mothers with an early dietary manipulation failed to prune gustatory terminal fields even though peripheral taste activity developed normally...
December 4, 2023: Journal of Experimental Medicine
https://read.qxmd.com/read/37728563/identifying-biomarkers-of-heterogeneity-and-transplantation-efficacy-in-retinal-pigment-epithelial-cells
#2
JOURNAL ARTICLE
Farhad Farjood, Justine D Manos, Yue Wang, Anne L Williams, Cuiping Zhao, Susan Borden, Nazia Alam, Glen Prusky, Sally Temple, Jeffrey H Stern, Nathan C Boles
Transplantation of retinal pigment epithelial (RPE) cells holds great promise for patients with retinal degenerative diseases, such as age-related macular degeneration. In-depth characterization of RPE cell product identity and critical quality attributes are needed to enhance efficacy and safety of replacement therapy strategies. Here, we characterized an adult RPE stem cell-derived (RPESC-RPE) cell product using bulk and single-cell RNA sequencing (scRNA-seq), assessing functional cell integration in vitro into a mature RPE monolayer and in vivo efficacy by vision rescue in the Royal College of Surgeons rats...
December 4, 2023: Journal of Experimental Medicine
https://read.qxmd.com/read/37725138/essential-role-of-the-pax5-c-terminal-domain-in-controlling-b-cell-commitment-and-development
#3
JOURNAL ARTICLE
Sarah Gruenbacher, Markus Jaritz, Louisa Hill, Markus Schäfer, Meinrad Busslinger
The B cell regulator Pax5 consists of multiple domains whose function we analyzed in vivo by deletion in Pax5. While B lymphopoiesis was minimally affected in mice with homozygous deletion of the octapeptide or partial homeodomain, both sequences were required for optimal B cell development. Deletion of the C-terminal regulatory domain 1 (CRD1) interfered with B cell development, while elimination of CRD2 modestly affected B-lymphopoiesis. Deletion of CRD1 and CRD2 arrested B cell development at an uncommitted pro-B cell stage...
December 4, 2023: Journal of Experimental Medicine
https://read.qxmd.com/read/37725372/lysosomal-cholesterol-overload-in-macrophages-promotes-liver-fibrosis-in-a-mouse-model-of-nash
#4
JOURNAL ARTICLE
Michiko Itoh, Atsushi Tamura, Sayaka Kanai, Miyako Tanaka, Yohei Kanamori, Ibuki Shirakawa, Ayaka Ito, Yasuyoshi Oka, Isao Hidaka, Taro Takami, Yasushi Honda, Mitsuyo Maeda, Yasuyuki Saito, Yoji Murata, Takashi Matozaki, Atsushi Nakajima, Yosky Kataoka, Tomoo Ogi, Yoshihiro Ogawa, Takayoshi Suganami
Accumulation of lipotoxic lipids, such as free cholesterol, induces hepatocyte death and subsequent inflammation and fibrosis in the pathogenesis of nonalcoholic steatohepatitis (NASH). However, the underlying mechanisms remain unclear. We have previously reported that hepatocyte death locally induces phenotypic changes in the macrophages surrounding the corpse and remnant lipids, thereby promoting liver fibrosis in a murine model of NASH. Here, we demonstrated that lysosomal cholesterol overload triggers lysosomal dysfunction and profibrotic activation of macrophages during the development of NASH...
November 6, 2023: Journal of Experimental Medicine
https://read.qxmd.com/read/37712948/hemifacial-myohyperplasia-is-due-to-somatic-muscular-pik3ca-gain-of-function-mutations-and-responds-to-pharmacological-inhibition
#5
JOURNAL ARTICLE
Charles Bayard, Eleonora Segna, Maxime Taverne, Antoine Fraissenon, Quentin Hennocq, Baptiste Periou, Lola Zerbib, Sophia Ladraa, Célia Chapelle, Clément Hoguin, Sophie Kaltenbach, Patrick Villarese, Vahid Asnafi, Christine Broissand, Ivan Nemazanyy, Gwennhael Autret, Nicolas Goudin, Christophe Legendre, François-Jérôme Authier, Thomas Viel, Bertrand Tavitian, Cyril Gitiaux, Sylvie Fraitag, Jean-Paul Duong, Clarisse Delcros, Bernard Sergent, Arnaud Picard, Michael Dussiot, Laurent Guibaud, Roman Khonsari, Guillaume Canaud
Hemifacial myohyperplasia (HFMH) is a rare cause of facial asymmetry exclusively involving facial muscles. The underlying cause and the mechanism of disease progression are unknown. Here, we identified a somatic gain-of-function mutation of PIK3CA in five pediatric patients with HFMH. To understand the physiopathology of muscle hypertrophy in this context, we created a mouse model carrying specifically a PIK3CA mutation in skeletal muscles. PIK3CA gain-of-function mutation led to striated muscle cell hypertrophy, mitochondria dysfunction, and hypoglycemia with low circulating insulin levels...
November 6, 2023: Journal of Experimental Medicine
https://read.qxmd.com/read/37703004/the-guanine-nucleotide-exchange-factor-rin-like-controls-tfh-cell-differentiation-via-cd28-signaling
#6
JOURNAL ARTICLE
Lisa Sandner, Marlis Alteneder, Ramona Rica, Barbara Woller, Eleonora Sala, Tobias Frey, Anela Tosevska, Ci Zhu, Moritz Madern, Matarr Khan, Pol Hoffmann, Alexandra Schebesta, Ichiro Taniuchi, Michael Bonelli, Klaus Schmetterer, Matteo Iannacone, Mirela Kuka, Wilfried Ellmeier, Shinya Sakaguchi, Ruth Herbst, Nicole Boucheron
T follicular helper (Tfh) cells are essential for the development of germinal center B cells and high-affinity antibody-producing B cells in humans and mice. Here, we identify the guanine nucleotide exchange factor (GEF) Rin-like (Rinl) as a negative regulator of Tfh generation. Loss of Rinl leads to an increase of Tfh in aging, upon in vivo immunization and acute LCMV Armstrong infection in mice, and in human CD4+ T cell in vitro cultures. Mechanistically, adoptive transfer experiments using WT and Rinl-KO naïve CD4+ T cells unraveled T cell-intrinsic GEF-dependent functions of Rinl...
November 6, 2023: Journal of Experimental Medicine
https://read.qxmd.com/read/37698554/nk-cell-expansion-requires-hur-and-mediates-control-of-solid-tumors-and-long-term-virus-infection
#7
JOURNAL ARTICLE
Sytse J Piersma, Sushant Bangru, Jeesang Yoon, Tom W Liu, Liping Yang, Chyi-Song Hsieh, Beatrice Plougastel-Douglas, Auinash Kalsotra, Wayne M Yokoyama
Natural killer (NK) cells are lymphocytes capable of controlling tumors and virus infections through direct lysis and cytokine production. While both T and NK cells expand and accumulate in affected tissues, the role of NK cell expansion in tumor and viral control is not well understood. Here, we show that posttranscriptional regulation by the RNA-binding protein HuR is essential for NK cell expansion without negatively affecting effector functions. HuR-deficient NK cells displayed defects in the metaphase of the cell cycle, including decreased expression and alternative splicing of Ska2, a component of the spindle and kinetochore complex...
November 6, 2023: Journal of Experimental Medicine
https://read.qxmd.com/read/37698553/allergen-exposure-functionally-alters-influenza-specific-cd4-th1-memory-cells-in-the-lung
#8
JOURNAL ARTICLE
Mikel J Rüterbusch, Brian D Hondowicz, Kennidy K Takehara, Kurt B Pruner, Thomas S Griffith, Marion Pepper
CD4+ lung-resident memory T cells (TRM) generated in response to influenza infection confer effective protection against subsequent viral exposures. Whether these cells can be altered by environmental antigens and cytokines released during heterologous, antigen-independent immune responses is currently unclear. We therefore investigated how influenza-specific CD4+ Th1 TRM in the lung are impacted by a subsequent Th2-inducing respiratory house dust mite (HDM) exposure. Although naïve influenza-specific CD4+ T cells in the lymph nodes do not respond to HDM, influenza-specific CD4+ TRM in the lungs do respond to a subsequent allergen exposure by decreasing expression of the transcription factor T-bet...
November 6, 2023: Journal of Experimental Medicine
https://read.qxmd.com/read/37695525/interleukin-22-suppresses-major-histocompatibility-complex-ii-in-mucosal-epithelial-cells
#9
JOURNAL ARTICLE
Md Moniruzzaman, M Arifur Rahman, Ran Wang, Kuan Yau Wong, Alice C-H Chen, Alexandra Mueller, Steven Taylor, Alexa Harding, Thishan Illankoon, Percival Wiid, Haressh Sajiir, Veronika Schreiber, Lucy D Burr, Michael A McGuckin, Simon Phipps, Sumaira Z Hasnain
Major histocompatibility complex (MHC) II is dynamically expressed on mucosal epithelial cells and is induced in response to inflammation and parasitic infections, upon exposure to microbiota, and is increased in chronic inflammatory diseases. However, the regulation of epithelial cell-specific MHC II during homeostasis is yet to be explored. We discovered a novel role for IL-22 in suppressing epithelial cell MHC II partially via the regulation of endoplasmic reticulum (ER) stress, using animals lacking the interleukin-22-receptor (IL-22RA1), primary human and murine intestinal and respiratory organoids, and murine models of respiratory virus infection or with intestinal epithelial cell defects...
November 6, 2023: Journal of Experimental Medicine
https://read.qxmd.com/read/37695524/il-22-immunity-s-bittersweet-symphony
#10
JOURNAL ARTICLE
Jinzhi Duan, Juan D Matute, Richard S Blumberg
Epithelial cells play a crucial role in barrier defense. Here, Moniruzzaman et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20230106) discovered that interleukin-22 (IL-22) represses MHC class II expression by epithelial cells with an opposite impact on chronic inflammatory disease and viral infection.
November 6, 2023: Journal of Experimental Medicine
https://read.qxmd.com/read/37695523/antigen-presenting-autoreactive-b-cells-activate-regulatory-t-cells-and-suppress-autoimmune-arthritis-in-mice
#11
JOURNAL ARTICLE
Mike Aoun, Ana Coelho, Alexander Krämer, Amit Saxena, Pierre Sabatier, Christian Michel Beusch, Erik Lönnblom, Manman Geng, Nhu-Nguyen Do, Zhongwei Xu, Jingdian Zhang, Yibo He, Laura Romero Castillo, Hassan Abolhassani, Bingze Xu, Johan Viljanen, Joanna Rorbach, Gonzalo Fernandez Lahore, Inger Gjertsson, Alf Kastbom, Christopher Sjöwall, Jan Kihlberg, Roman A Zubarev, Harald Burkhardt, Rikard Holmdahl
B cells undergo several rounds of selection to eliminate potentially pathogenic autoreactive clones, but in contrast to T cells, evidence of positive selection of autoreactive B cells remains moot. Using unique tetramers, we traced natural autoreactive B cells (C1-B) specific for a defined triple-helical epitope on collagen type-II (COL2), constituting a sizeable fraction of the physiological B cell repertoire in mice, rats, and humans. Adoptive transfer of C1-B suppressed arthritis independently of IL10, separating them from IL10-secreting regulatory B cells...
November 6, 2023: Journal of Experimental Medicine
https://read.qxmd.com/read/37642942/a-novel-molecular-class-that-recruits-hdac-mecp2-complexes-to-pu-1-motifs-reduces-neuroinflammation
#12
JOURNAL ARTICLE
William T Ralvenius, Alison E Mungenast, Hannah Woolf, Margaret M Huston, Tyler Z Gillingham, Stephen K Godin, Jay Penney, Hugh P Cam, Fan Gao, Celia G Fernandez, Barbara Czako, Yaima Lightfoot, William J Ray, Adrian Beckmann, Alison M Goate, Edoardo Marcora, Carmen Romero-Molina, Pinar Ayata, Anne Schaefer, Elizabeta Gjoneska, Li-Huei Tsai
Pervasive neuroinflammation occurs in many neurodegenerative diseases, including Alzheimer's disease (AD). SPI1/PU.1 is a transcription factor located at a genome-wide significant AD-risk locus and its reduced expression is associated with delayed onset of AD. We analyzed single-cell transcriptomic datasets from microglia of human AD patients and found an enrichment of PU.1-binding motifs in the differentially expressed genes. In hippocampal tissues from transgenic mice with neurodegeneration, we found vastly increased genomic PU...
November 6, 2023: Journal of Experimental Medicine
https://read.qxmd.com/read/37642941/myc-is-a-clinically-significant-driver-of-mtor-inhibitor-resistance-in-breast-cancer
#13
JOURNAL ARTICLE
Jinhyuk Bhin, Julia Yemelyanenko, Xue Chao, Sjoerd Klarenbeek, Mark Opdam, Yuval Malka, Liesbeth Hoekman, Dinja Kruger, Onno Bleijerveld, Chiara S Brambillasca, Justin Sprengers, Bjørn Siteur, Stefano Annunziato, Matthijs J van Haren, Nathaniel I Martin, Marieke van de Ven, Dennis Peters, Reuven Agami, Sabine C Linn, Epie Boven, Maarten Altelaar, Jos Jonkers, Daniel Zingg, Lodewyk F A Wessels
Targeting the PI3K-AKT-mTOR pathway is a promising therapeutic strategy for breast cancer treatment. However, low response rates and development of resistance to PI3K-AKT-mTOR inhibitors remain major clinical challenges. Here, we show that MYC activation drives resistance to mTOR inhibitors (mTORi) in breast cancer. Multiomic profiling of mouse invasive lobular carcinoma (ILC) tumors revealed recurrent Myc amplifications in tumors that acquired resistance to the mTORi AZD8055. MYC activation was associated with biological processes linked to mTORi response and counteracted mTORi-induced translation inhibition by promoting translation of ribosomal proteins...
November 6, 2023: Journal of Experimental Medicine
https://read.qxmd.com/read/37624388/defective-lat-signalosome-pathology-in-mice-mimics-human-igg4-related-disease-at-single-cell-level
#14
JOURNAL ARTICLE
Anais Joachim, Rudy Aussel, Léna Gélard, Fanghui Zhang, Daiki Mori, Claude Grégoire, Sergio Villazala Merino, Mauro Gaya, Yinming Liang, Marie Malissen, Bernard Malissen
Mice with a loss-of-function mutation in the LAT adaptor (LatY136F) develop an autoimmune and type 2 inflammatory disorder called defective LAT signalosome pathology (DLSP). We analyzed via single-cell omics the trajectory leading to LatY136F DLSP and the underlying CD4+ T cell diversification. T follicular helper cells, CD4+ cytotoxic T cells, activated B cells, and plasma cells were found in LatY136F spleen and lung. Such cell constellation entailed all the cell types causative of human IgG4-related disease (IgG4-RD), an autoimmune and inflammatory condition with LatY136F DLSP-like histopathological manifestations...
November 6, 2023: Journal of Experimental Medicine
https://read.qxmd.com/read/37615937/trained-immunity-of-alveolar-macrophages-enhances-injury-resolution-via-klf4-mertk-mediated-efferocytosis
#15
JOURNAL ARTICLE
Sreeparna Chakraborty, Abhalaxmi Singh, Li Wang, Xinge Wang, Mark A Sanborn, Zijing Ye, Mark Maienschein-Cline, Amitabha Mukhopadhyay, Balaji B Ganesh, Asrar B Malik, Jalees Rehman
Recent studies suggest that training of innate immune cells such as tissue-resident macrophages by repeated noxious stimuli can heighten host defense responses. However, it remains unclear whether trained immunity of tissue-resident macrophages also enhances injury resolution to counterbalance the heightened inflammatory responses. Here, we studied lung-resident alveolar macrophages (AMs) prechallenged with either the bacterial endotoxin or with Pseudomonas aeruginosa and observed that these trained AMs showed greater resilience to pathogen-induced cell death...
November 6, 2023: Journal of Experimental Medicine
https://read.qxmd.com/read/37615936/hematopoietic-specific-heterozygous-loss-of-dnmt3a-exacerbates-colitis-associated-colon-cancer
#16
JOURNAL ARTICLE
Yang Feng, Qingchen Yuan, Rachel C Newsome, Troy Robinson, Robert L Bowman, Ashley N Zuniga, Kendra N Hall, Cassandra M Bernsten, Daniil E Shabashvili, Kathryn I Krajcik, Chamara Gunaratne, Zachary J Zaroogian, Kartika Venugopal, Heidi L Casellas Roman, Ross L Levine, Walid K Chatila, Rona Yaeger, Alberto Riva, Christian Jobin, Daniel Kopinke, Dorina Avram, Olga A Guryanova
Clonal hematopoiesis (CH) is defined as clonal expansion of mutant hematopoietic stem cells absent diagnosis of a hematologic malignancy. Presence of CH in solid tumor patients, including colon cancer, correlates with shorter survival. We hypothesized that bone marrow-derived cells with heterozygous loss-of-function mutations of DNMT3A, the most common genetic alteration in CH, contribute to the pathogenesis of colon cancer. In a mouse model that combines colitis-associated colon cancer (CAC) with experimental CH driven by Dnmt3a+/Δ, we found higher tumor penetrance and increased tumor burden compared with controls...
November 6, 2023: Journal of Experimental Medicine
https://read.qxmd.com/read/37606887/network-analysis-identifies-strain-dependent-response-to-tau-and-tau-seeding-associated-genes
#17
JOURNAL ARTICLE
Dominic J Acri, Yanwen You, Mason D Tate, Hande Karahan, Pablo Martinez, Brianne McCord, A Daniel Sharify, Sutha John, Byungwook Kim, Luke C Dabin, Stéphanie Philtjens, H R Sagara Wijeratne, Tyler J McCray, Daniel C Smith, Stephanie J Bissel, Bruce T Lamb, Cristian A Lasagna-Reeves, Jungsu Kim
Previous research demonstrated that genetic heterogeneity is a critical factor in modeling amyloid accumulation and other Alzheimer's disease phenotypes. However, it is unknown what mechanisms underlie these effects of genetic background on modeling tau aggregate-driven pathogenicity. In this study, we induced tau aggregation in wild-derived mice by expressing MAPT. To investigate the effect of genetic background on the action of tau aggregates, we performed RNA sequencing with brains of C57BL/6J, CAST/EiJ, PWK/PhJ, and WSB/EiJ mice (n = 64) and determined core transcriptional signature conserved in all genetic backgrounds and signature unique to wild-derived backgrounds...
November 6, 2023: Journal of Experimental Medicine
https://read.qxmd.com/read/37584653/il-6-translation-is-a-therapeutic-target-of-human-cytokine-release-syndrome
#18
JOURNAL ARTICLE
Yuzhuo Yang, Yajing Zhang, Xiaoyan Xing, Gang Xu, Xin Lin, Yao Wang, Meixia Chen, Chunmeng Wang, Bin Zhang, Weidong Han, Xiaoyu Hu
Chimeric antigen receptor (CAR) T therapies have achieved remarkable success for treating hematologic malignancies, yet are often accompanied by severe cytokine release syndrome (CRS). Here, an accidental clinical observation raised the possibility that metoprolol, an FDA-approved β1 adrenergic receptor blocker widely used for cardiovascular conditions, may alleviate CAR T-induced CRS. Metoprolol effectively blocked IL-6 production in human monocytes through unexpected mechanisms of action of targeting IL-6 protein translation but not IL6 mRNA expression...
November 6, 2023: Journal of Experimental Medicine
https://read.qxmd.com/read/37728758/women-in-stem-becoming-independent-great-mentors-make-all-the-difference
#19
JOURNAL ARTICLE
Lucie Van Emmenis
No abstract text is available yet for this article.
October 2, 2023: Journal of Experimental Medicine
https://read.qxmd.com/read/37725354/nina-cabezas-wallscheid-enjoying-the-freedom-to-decide-my-research-path
#20
JOURNAL ARTICLE
Lucie Van Emmenis
Nina Cabezas Wallscheid is a group leader at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, Germany. Taking a multidisciplinary approach, her lab investigates the mechanisms by which metabolites regulate the epigenetic and metabolic state of hematopoietic stem cell fate in young and upon aging, with the aim to identify therapeutic strategies for nutritional and hematological diseases. We spoke to Nina recently to learn more about her long-term interest in cell regulation, the joys of being a group leader, and the adventures she goes on while outside of the lab...
October 2, 2023: Journal of Experimental Medicine
journal
journal
25530
1
2
Fetch more papers »
Fetching more papers... Fetching...
Remove bar
Read by QxMD icon Read
×

Save your favorite articles in one place with a free QxMD account.

×

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"

We want to hear from doctors like you!

Take a second to answer a survey question.