Issues
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Cover Image
Cover Image
ON THE COVER
Regulation of pulmonary plasma cell responses during secondary infection with influenza virus is largely independent of CD4+ and CD8+ T cells. The image shows a representative image from thick sections of lungs of BAT mice reinfected with influenza and depleted for CD4+ T cells, showing the positioning of alveoli-associated plasma cells (AlvPC) in rechallenged lungs. The mice were genetically engineered and labeled as follows: AID-tdTo-mato (red), Blimp-1mVenus (yellow), CFP-Flu (light blue), collagen (SH) (purple). Image © MacLean et al., 2024. https://doi.org/10.1084/jem.20232014 - PDF Icon PDF LinkTable of Contents
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People & Ideas
Linda-Gail Bekker: Mentorship is critical for anyone in STEM
Linda-Gail Bekker is a professor, chief executive officer of the Desmond Tutu HIV Foundation, and director of the Desmond Tutu HIV Centre at the Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa. Her research interests include HIV treatment and prevention and tuberculosis, and she is active in developing community projects to promote education and research. We talked to Linda-Gail about her career, the importance of mentorship, and how rewarding it is to collaborate, mentor, and uplift other scientists.
Insights
Stress relief of chemo illness
Hepatic IRE1α-XBP1 signaling boosts GDF15-triggered appetite suppression and weight reduction in chemotherapy.
Send it, receive it, quick erase it: A mouse model to decipher chemokine communication
In this issue of JEM, Rodrigo et al. characterize a novel class of dual fluorescence reporter mice that helps with the identification of cells that produce and/or sense a given chemokine in vitro and in vivo.
γδ T cells: The first line of defense for neonates
In this issue of JEM, León-Lara et al. investigate the role and function of human γδ T cells in sepsis from the blood of a novel longitudinal cohort of preterm infants.
Viewpoint
Women in STEM becoming independent: The journey to independence is an immensely gratifying odyssey
This year at JEM, we are highlighting women in science by sharing their stories and amplifying their voices. In this Viewpoint, we hear from a cross section of women, across multiple research fields, discussing their science and the process of setting up a lab as an independent researcher.
Reviews
Radiotherapy and immunology
The majority of cancer patients receive radiotherapy. Wang et al. review preclinical and clinical data related to the importance of immune responses to radiotherapy-induced anti-tumor effects, as well as blockade of immune checkpoints PD-1/PD-L1 and/or CTLA-4 in combination with radiotherapy.
Brief Definitive Reports
Hepatic IRE1α-XBP1 signaling promotes GDF15-mediated anorexia and body weight loss in chemotherapy
Tang et al. demonstrate that hepatic IRE1α acts as a molecular driver of GDF15-mediated anorexia, and blocking IRE1α activity offers a potential therapeutic approach to alleviate anorexia in chemotherapy.
Regulation of pulmonary plasma cell responses during secondary infection with influenza virus
The authors show that following influenza virus rechallenge, lung resident, but not circulating memory B cells differentiate into PCs near infected alveoli. In these sites, outside of iBALTs, BRM cells’ activation is regulated by innate cells and signals.
Technical Advances and Resources
Dual fluorescence reporter mice for Ccl3 transcription, translation, and intercellular communication
Dual fluorescence reporter mice were developed to identify cells that secrete and/or sense chemokines and to delete producing cells. Thereby, the authors found that the chemokine Ccl3 facilitates auto/paracrine NK cell crosstalk to amplify their response against cytomegalovirus infection.
Articles
γδ T cell profiling in a cohort of preterm infants reveals elevated frequencies of CD83+ γδ T cells in sepsis
Léon-Lara et al. define age-driven postnatal adaptation of γδ T cells and identify CD83+ γδ T cells in preterm infants with sepsis. CD83 expression specifically relates to neonatal γδ T cells and points to functional diversity of neonatal γδ T cells in this inflammatory setting.
Intestinal cDC1s provide cues required for CD4+ T cell–mediated resistance to Cryptosporidium
Cryptosporidium is an enteric pathogen that is a major cause of diarrheal disease worldwide. In this work, the authors engineer transgenic C. parvum to express MHCII-restricted model antigens and thereby dissect priming and effector functions in parasite-specific CD4+ T cells.
Patients and mice with deficiency in the SNARE protein SYNTAXIN-11 have a secondary B cell defect
CD4 T helper cells use the SNARE protein SYNTAXIN-11 to promote B cell differentiation, germinal center formation, and class switching by facilitating CD40L mobilization and IL-2 and IL-10 secretion. Variable hypogammaglobulinemia is a novel phenotype of human STX11 deficiency.
Csk restrains BCR-mediated ROS production and contributes to germinal center selection and affinity maturation
Inoue et al. show that an augmentation of BCR signaling in GC B cells by inducible depletion of Csk results in decreased GC B cell competitiveness and impaired affinity maturation, partly due to enhanced ROS-mediated apoptosis.
PD-L1 promotes oncolytic virus infection via a metabolic shift that inhibits the type I IFN pathway
Cell-intrinsic PD-L1 signaling inhibits the type I interferon pathway in cancer cells via a mechanism that involves metabolic alterations. PD-L1 activity is triggered by a variety of stimuli, including PD-L1 antibodies, and ultimately increases the efficacy of oncolytic virus therapy.
Act1 drives chemoresistance via regulation of antioxidant RNA metabolism and redox homeostasis
Hong et al. report that IL-17/Act1 induces chemoresistance by modulating redox homeostasis through epitranscriptomic regulation of antioxidant RNA metabolism. Antisense oligonucleotide that specifically disrupts Act1’s binding to Wtap mRNA inhibits IL-17/Act1–WTAP-mediated antioxidant protein production, offering a potential therapeutic strategy for chemoresistance.
TET2–STAT3–CXCL5 nexus promotes neutrophil lipid transfer to fuel lung adeno-to-squamous transition
Adeno-to-squamous transition drives therapeutic resistance in LKB1-mutant lung cancer. Here, Xue et al. uncover a TET2-mediated epigenetic mechanism in controlling such phenotypic transition via promoting neutrophil infiltration and neutrophil-to-cancer cell lipid transfer and identify therapeutic strategies to control phenotypic transition.
Corrections
Correction: Patients and mice with deficiency in the SNARE protein SYNTAXIN-11 have a secondary B cell defect
Correction: TET2–STAT3–CXCL5 nexus promotes neutrophil lipid transfer to fuel lung adeno-to-squamous transition
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