Use the journals feature with a free QxMD account.
Use Read by QxMD to access full text via your institution or open access sources.
Read also provides personalized recommendations to keep you up to date in your field.
Existing User
Sign InNew to Read
Sign Up#1
JOURNAL ARTICLE
Chong Zuo, John M Baer, Brett L Knolhoff, Jad I Belle, Xiuting Liu, Angela Alarcon De La Lastra, Christina Fu, Graham D Hogg, Natalie L Kingston, Marcus A Breden, Paarth B Dodhiawala, Daniel Cui Zhou, Varintra E Lander, C Alston James, Li Ding, Kian-Huat Lim, Ryan C Fields, William G Hawkins, Jason D Weber, Guoyan Zhao, David G DeNardo
Tumor-associated macrophages (TAMs) are abundant in pancreatic ductal adenocarcinomas (PDACs). While TAMs are known to proliferate in cancer tissues, the impact of this on macrophage phenotype and disease progression is poorly understood. We showed that in PDAC, proliferation of TAMs could be driven by colony stimulating factor-1 (CSF1) produced by cancer-associated fibroblasts. CSF1 induced high levels of p21 in macrophages, which regulated both TAM proliferation and phenotype. TAMs in human and mouse PDACs with high levels of p21 had more inflammatory and immunosuppressive phenotypes...
June 5, 2023: Journal of Experimental Medicine
#2
JOURNAL ARTICLE
Kavita Rawat, Anita Tewari, Xin Li, Arlind B Mara, William T King, Sophie L Gibbings, Chinaza F Nnam, Fred W Kolling, Bart N Lambrecht, Claudia V Jakubzick
Dendritic cells (DCs) and monocytes capture, transport, and present antigen to cognate T cells in the draining lymph nodes (LNs) in a CCR7-dependent manner. Since only migratory DCs express this chemokine receptor, it is unclear how monocytes reach the LN. In steady-state and following inhalation of several PAMPs, scRNA-seq identified LN mononuclear phagocytes as monocytes, resident, or migratory type 1 and type 2 conventional (c)DCs, despite the downregulation of Xcr1, Clec9a, H2-Ab1, Sirpa, and Clec10a transcripts on migratory cDCs...
June 5, 2023: Journal of Experimental Medicine
#3
JOURNAL ARTICLE
Tina Nguyen, Anthony Lau, Julia Bier, Kristen C Cooke, Helen Lenthall, Stephanie Ruiz-Diaz, Danielle T Avery, Henry Brigden, David Zahra, William A Sewell, Luke Droney, Satoshi Okada, Takaki Asano, Hassan Abolhassani, Zahra Chavoshzadeh, Roshini S Abraham, Nipunie Rajapakse, Eric W Klee, Joseph A Church, Andrew Williams, Melanie Wong, Christoph Burkhart, Gulbu Uzel, David R Croucher, David E James, Cindy S Ma, Robert Brink, Stuart G Tangye, Elissa K Deenick
Heterozygous loss-of-function (LOF) mutations in PIK3R1 (encoding phosphatidylinositol 3-kinase [PI3K] regulatory subunits) cause activated PI3Kδ syndrome 2 (APDS2), which has a similar clinical profile to APDS1, caused by heterozygous gain-of-function (GOF) mutations in PIK3CD (encoding the PI3K p110δ catalytic subunit). While several studies have established how PIK3CD GOF leads to immune dysregulation, less is known about how PIK3R1 LOF mutations alter cellular function. By studying a novel CRISPR/Cas9 mouse model and patients' immune cells, we determined how PIK3R1 LOF alters cellular function...
June 5, 2023: Journal of Experimental Medicine
#4
JOURNAL ARTICLE
Lore Billiet, Laurenz De Cock, Guillem Sanchez Sanchez, Rupert L Mayer, Glenn Goetgeluk, Stijn De Munter, Melissa Pille, Joline Ingels, Hanne Jansen, Karin Weening, Eva Pascal, Killian Raes, Sarah Bonte, Tessa Kerre, Niels Vandamme, Ruth Seurinck, Jana Roels, Marieke Lavaert, Filip Van Nieuwerburgh, Georges Leclercq, Tom Taghon, Francis Impens, Björn Menten, David Vermijlen, Bart Vandekerckhove
In the human thymus, a CD10+ PD-1+ TCRαβ+ differentiation pathway diverges from the conventional single positive T cell lineages at the early double-positive stage. Here, we identify the progeny of this unconventional lineage in antigen-inexperienced blood. These unconventional T cells (UTCs) in thymus and blood share a transcriptomic profile, characterized by hallmark transcription factors (i.e., ZNF683 and IKZF2), and a polyclonal TCR repertoire with autoreactive features, exhibiting a bias toward early TCRα chain rearrangements...
June 5, 2023: Journal of Experimental Medicine
#5
JOURNAL ARTICLE
Keenan A Lacey, Lee Serpas, Sohei Makita, Yueyang Wang, Ali Rashidfarrokhi, Chetna Soni, Sandra Gonzalez, Andre Moreira, Victor J Torres, Boris Reizis
Extracellular DNase DNASE1L3 maintains tolerance to self-DNA in humans and mice, whereas the role of its homolog DNASE1 remains controversial, and the overall function of secreted DNases in immunity is unclear. We report that deletion of murine DNASE1 neither caused autoreactivity in isolation nor exacerbated lupus-like disease in DNASE1L3-deficient mice. However, combined deficiency of DNASE1 and DNASE1L3 rendered mice susceptible to bloodstream infection with Staphylococcus aureus. DNASE1/DNASE1L3 double-deficient mice mounted a normal innate response to S...
June 5, 2023: Journal of Experimental Medicine
#6
JOURNAL ARTICLE
Andrew J Sawyer, Ellis Patrick, Jarem Edwards, James S Wilmott, Timothy Fielder, Qianting Yang, Daniel L Barber, Joel D Ernst, Warwick J Britton, Umaimainthan Palendira, Xinchun Chen, Carl G Feng
The hallmark of tuberculosis (TB) is the formation of immune cell-enriched aggregates called granulomas. While granulomas are pathologically diverse, their tissue-wide heterogeneity has not been spatially resolved at the single-cell level in human tissues. By spatially mapping individual immune cells in every lesion across entire tissue sections, we report that in addition to necrotizing granulomas, the human TB lung contains abundant non-necrotizing leukocyte aggregates surrounding areas of necrotizing tissue...
June 5, 2023: Journal of Experimental Medicine
#7
JOURNAL ARTICLE
Hesham D Abdulla, Raed Alserihi, Christoffer Flensburg, Waruni Abeysekera, Meng-Xiao Luo, Daniel H D Gray, Xiaodong Liu, Gordon K Smyth, Warren S Alexander, Ian J Majewski, Matthew P McCormack
Cell competition has recently emerged as an important tumor suppressor mechanism in the thymus that inhibits autonomous thymic maintenance. Here, we show that the oncogenic transcription factor Lmo2 causes autonomous thymic maintenance in transgenic mice by inhibiting early T cell differentiation. This autonomous thymic maintenance results in the development of self-renewing preleukemic stem cells (pre-LSCs) and subsequent leukemogenesis, both of which are profoundly inhibited by restoration of thymic competition or expression of the antiapoptotic factor BCL2...
June 5, 2023: Journal of Experimental Medicine
#8
JOURNAL ARTICLE
Romane Thouenon, Loïc Chentout, Nidia Moreno-Corona, Lucie Poggi, Emilia Puig Lombardi, Benedicte Hoareau, Yohann Schmitt, Chantal Lagresle-Peyrou, Jacinta Bustamante, Isabelle André, Marina Cavazzana, Anne Durandy, Jean-Laurent Casanova, Lionel Galicier, Jehane Fadlallah, Alain Fischer, Sven Kracker
Here, we report on a heterozygous interferon regulatory factor 4 (IRF4) missense variant identified in three patients from a multigeneration family with hypogammaglobulinemia. Patients' low blood plasmablast/plasma cell and naïve CD4 and CD8 T cell counts contrasted with high terminal effector CD4 and CD8 T cell counts. Expression of the mutant IRF4 protein in control lymphoblastoid B cell lines reduced the expression of BLIMP-1 and XBP1 (key transcription factors in plasma cell differentiation). In B cell lines, the mutant IRF4 protein as wildtype was found to bind to known IRF4 binding motifs...
June 5, 2023: Journal of Experimental Medicine
#9
JOURNAL ARTICLE
Samuel W Du, Krzysztof Palczewski
CRISPR/Cas9 genome editing techniques have the potential to treat previously untreatable inherited genetic disorders of vision by correcting mutations that cause these afflictions. Using a prime editor, Qin et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20220776) restored visual functions in a mouse model (rd10) of retinitis pigmentosa.
May 1, 2023: Journal of Experimental Medicine
#10
JOURNAL ARTICLE
Huan Qin, Wenliang Zhang, Shiyao Zhang, Yuan Feng, Weihui Xu, Jia Qi, Qian Zhang, Chunxiu Xu, Shanshan Liu, Jia Zhang, Yushuang Lei, Wanqin Liu, Shuyu Feng, Jingjing Wang, Xuefei Fu, Zifen Xu, Ping Li, Kai Yao
Retinitis pigmentosa (RP) is an inherited retinal dystrophy causing progressive and irreversible loss of retinal photoreceptors. Here, we developed a genome-editing tool characterized by the versatility of prime editors (PEs) and unconstrained PAM requirement of a SpCas9 variant (SpRY), referred to as PESpRY. The diseased retinas of Pde6b-associated RP mouse model were transduced via a dual AAV system packaging PESpRY for the in vivo genome editing through a non-NGG PAM (GTG). The progressing cell loss was reversed once the mutation was corrected, leading to substantial rescue of photoreceptors and production of functional PDE6β...
May 1, 2023: Journal of Experimental Medicine
#11
JOURNAL ARTICLE
Keitaro Fukuda
In this issue of JEM, Reijers et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20221952) demonstrate that pre- and post-treatment IFNγ-related gene expression scores are promising markers for choosing neoadjuvant immunotherapy for stage III melanoma.
May 1, 2023: Journal of Experimental Medicine
#12
JOURNAL ARTICLE
Irene L M Reijers, Disha Rao, Judith M Versluis, Alexander M Menzies, Petros Dimitriadis, Michel W Wouters, Andrew J Spillane, Willem M C Klop, Annegien Broeks, Linda J W Bosch, Marta Lopez-Yurda, Winan J van Houdt, Robert V Rawson, Lindsay G Grijpink-Ongering, Maria Gonzalez, Sten Cornelissen, Jasper Bouwman, Joyce Sanders, Elsemieke Plasmeijer, Yannick S Elshot, Richard A Scolyer, Bart A van de Wiel, Daniel S Peeper, Alexander C J van Akkooi, Georgina V Long, Christian U Blank
Neoadjuvant ipilimumab + nivolumab has demonstrated high pathologic response rates in stage III melanoma. Patients with low intra-tumoral interferon-γ (IFN-γ) signatures are less likely to benefit. We show that domatinostat (a class I histone deacetylase inhibitor) addition to anti-PD-1 + anti-CTLA-4 increased the IFN-γ response and reduced tumor growth in our murine melanoma model, rationalizing evaluation in patients. To stratify patients into IFN-γ high and low cohorts, we developed a baseline IFN-γ signature expression algorithm, which was prospectively tested in the DONIMI trial...
May 1, 2023: Journal of Experimental Medicine
#13
EDITORIAL
Maximilian Heeg, Ananda W Goldrath
In this issue of JEM, Qiu et al. (2023. J. Exp. Med. https://doi.org/10.1084/jem.20210923) show that retinoic acid signaling during priming in the mesenteric lymph node licenses CD8+ T cells to develop into small intestinal tissue-resident memory cells, a finding that provides key insights into tissue-specific vaccination strategies.
May 1, 2023: Journal of Experimental Medicine
#14
JOURNAL ARTICLE
Mehul Sharma, Daniel Leung, Mana Momenilandi, Lauren C W Jones, Lucia Pacillo, Alyssa E James, Jill R Murrell, Selket Delafontaine, Jesmeen Maimaris, Maryam Vaseghi-Shanjani, Kate L Del Bel, Henry Y Lu, Gilbert T Chua, Silvia Di Cesare, Oriol Fornes, Zhongyi Liu, Gigliola Di Matteo, Maggie P Fu, Donato Amodio, Issan Yee San Tam, Gavin Shueng Wai Chan, Ashish A Sharma, Joshua Dalmann, Robin van der Lee, Géraldine Blanchard-Rohner, Susan Lin, Quentin Philippot, Phillip A Richmond, Jessica J Lee, Allison Matthews, Michael Seear, Alexandra K Turvey, Rachael L Philips, Terri F Brown-Whitehorn, Christopher J Gray, Kosuke Izumi, James R Treat, Kathleen H Wood, Justin Lack, Asya Khleborodova, Julie E Niemela, Xingtian Yang, Rui Liang, Lin Kui, Christina Sze Man Wong, Grace Wing Kit Poon, Alexander Hoischen, Caspar I van der Made, Jing Yang, Koon Wing Chan, Jaime Sou Da Rosa Duque, Pamela Pui Wah Lee, Marco Hok Kung Ho, Brian Hon Yin Chung, Huong Thi Minh Le, Wanling Yang, Pejman Rohani, Ali Fouladvand, Hassan Rokni-Zadeh, Majid Changi-Ashtiani, Mohammad Miryounesi, Anne Puel, Mohammad Shahrooei, Andrea Finocchi, Paolo Rossi, Beatrice Rivalta, Cristina Cifaldi, Antonio Novelli, Chiara Passarelli, Stefania Arasi, Dominique Bullens, Kate Sauer, Tania Claeys, Catherine M Biggs, Emma C Morris, Sergio D Rosenzweig, John J O'Shea, Wyeth W Wasserman, H Melanie Bedford, Clara D M van Karnebeek, Paolo Palma, Siobhan O Burns, Isabelle Meyts, Jean-Laurent Casanova, Jonathan J Lyons, Nima Parvaneh, Anh Thi Van Nguyen, Caterina Cancrini, Jennifer Heimall, Hanan Ahmed, Margaret L McKinnon, Yu Lung Lau, Vivien Béziat, Stuart E Turvey
STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds)...
May 1, 2023: Journal of Experimental Medicine
#15
JOURNAL ARTICLE
Yu-Chen Wang, Yang Cao, Calvin Pan, Zhiqiang Zhou, Lili Yang, Aldons J Lusis
The small intestine plays a key role in immunity and mediates inflammatory responses to high fat diets. We have used single-cell RNA-sequencing (scRNA-seq) and statistical modeling to examine gaps in our understanding of the dynamic properties of intestinal cells and underlying cellular mechanisms. Our scRNA-seq and flow cytometry studies of different layers of intestinal cells revealed new cell subsets and modeled developmental trajectories of intestinal intraepithelial lymphocytes, lamina propria lymphocytes, conventional dendritic cells, and enterocytes...
May 1, 2023: Journal of Experimental Medicine
#16
JOURNAL ARTICLE
Alexander D Daley, Cécile Bénézech
Milky spots of the omentum enable lymphocyte access to the peritoneal cavity. In this issue of JEM, Yoshihara and Okabe (2023. J. Exp. Med.https://doi.org/10.1084/jem.20221813) demonstrate how secretion of retinoic acid by fibroblastic reticular cells allows lymphocyte entry into milky spots and the peritoneal cavity.
May 1, 2023: Journal of Experimental Medicine
#17
JOURNAL ARTICLE
Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia.
Ana García-García, Rebeca Pérez de Diego, Carlos Flores, Darawan Rinchai, Jordi Solé-Violán, Àngela Deyà-Martínez, Blanca García-Solis, José M Lorenzo-Salazar, Elisa Hernández-Brito, Anna-Lisa Lanz, Leen Moens, Giorgia Bucciol, Mohamed Almuqamam, Joseph B Domachowske, Elena Colino, Juan Luis Santos-Perez, Francisco M Marco, Claudio Pignata, Aziz Bousfiha, Stuart E Turvey, Stefanie Bauer, Filomeen Haerynck, Javier Gonzalo Ocejo-Vinyals, Francisco Lendinez, Seraina Prader, Nora Naumann-Bartsch, Jana Pachlopnik Schmid, Catherine M Biggs, Kyla Hildebrand, Alexandra Dreesman, Miguel Ángel Cárdenes, Fatima Ailal, Ibtihal Benhsaien, Giuliana Giardino, Agueda Molina-Fuentes, Claudia Fortuny, Swetha Madhavarapu, Daniel H Conway, Carolina Prando, Laire Schidlowski, María Teresa Martínez de Saavedra Álvarez, Rafael Alfaro, Felipe Rodríguez de Castro, Isabelle Meyts, Fabian Hauck, Anne Puel, Paul Bastard, Bertrand Boisson, Emmanuelle Jouanguy, Laurent Abel, Aurélie Cobat, Qian Zhang, Jean-Laurent Casanova, Laia Alsina, Carlos Rodríguez-Gallego
X-linked recessive deficiency of TLR7, a MyD88- and IRAK-4-dependent endosomal ssRNA sensor, impairs SARS-CoV-2 recognition and type I IFN production in plasmacytoid dendritic cells (pDCs), thereby underlying hypoxemic COVID-19 pneumonia with high penetrance. We report 22 unvaccinated patients with autosomal recessive MyD88 or IRAK-4 deficiency infected with SARS-CoV-2 (mean age: 10.9 yr; 2 mo to 24 yr), originating from 17 kindreds from eight countries on three continents. 16 patients were hospitalized: six with moderate, four with severe, and six with critical pneumonia, one of whom died...
May 1, 2023: Journal of Experimental Medicine
#18
EDITORIAL
Bogdan Popescu, Kevin Shannon
Allosteric SHP2 inhibitors are a novel class of compounds that target hyperactive Ras/Mitogen Activated Protein Kinase (MAPK) signaling. In this issue of JEM, Wei et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20221563) report a genome-wide CRISPR/Cas9 knockout screen that uncovered novel mechanisms of adaptive resistance to pharmacologic inhibition of SHP2.
May 1, 2023: Journal of Experimental Medicine
#19
JOURNAL ARTICLE
Tomomi Yoshihara, Yasutaka Okabe
Lymphoid clusters in visceral adipose tissue omentum, known as milky spots, play a central role in the immunological defense in the abdomen. Milky spots exhibit hybrid nature between secondary lymph organs and ectopic lymphoid tissues, yet their development and maturation mechanisms are poorly understood. Here, we identified a subset of fibroblastic reticular cells (FRCs) that are uniquely present in omental milky spots. These FRCs were characterized by the expression of retinoic acid-converting enzyme, Aldh1a2, and endothelial cell marker, Tie2, in addition to canonical FRC-associated genes...
May 1, 2023: Journal of Experimental Medicine
#20
JOURNAL ARTICLE
Debolina Ganguly, Marcel O Schmidt, Morgan Coleman, Tuong-Vi Cindy Ngo, Noah Sorrelle, Adrian T A Dominguez, Gilbert Z Murimwa, Jason E Toombs, Cheryl Lewis, Yisheng V Fang, Fatima Valdes-Mora, David Gallego-Ortega, Anton Wellstein, Rolf A Brekken
Metastatic cancer cells adapt to thrive in secondary organs. To investigate metastatic adaptation, we performed transcriptomic analysis of metastatic and non-metastatic murine breast cancer cells. We found that pleiotrophin (PTN), a neurotrophic cytokine, is a metastasis-associated factor that is expressed highly by aggressive breast cancers. Moreover, elevated PTN in plasma correlated significantly with metastasis and reduced survival of breast cancer patients. Mechanistically, we find that PTN activates NF-κB in cancer cells leading to altered cytokine production, subsequent neutrophil recruitment, and an immune suppressive microenvironment...
May 1, 2023: Journal of Experimental Medicine
Make the most of Read.
Download the mobile app.
Download the mobile app.
Fetching more papers... 
