Journal of Experimental Medicine
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#1Nouraiz Ahmed (ETH Zurich: ETH Zurich)H-Index: 6
#2Martin Etzrodt (ETH Zurich: ETH Zurich)H-Index: 18
Last. Timm Schroeder (ETH Zurich: ETH Zurich)H-Index: 39
view all 13 authors...
Transcription factors (TFs) regulate cell fates, and their expression must be tightly regulated. Autoregulation is assumed to regulate many TFs' own expression to control cell fates. Here, we manipulate and quantify the (auto)regulation of PU.1, a TF controlling hematopoietic stem and progenitor cells (HSPCs), and correlate it to their future fates. We generate transgenic mice allowing both inducible activation of PU.1 and noninvasive quantification of endogenous PU.1 protein expression. The qua...
#1Kaitlin A. Read (OSU: The Ohio State University)H-Index: 2
#2Kenneth J Oestreich (OSU: The Ohio State University)H-Index: 3
For over a decade, mutual antagonism between the transcriptional repressors Bcl-6 and Blimp-1 has been appreciated as a key mechanistic determinant of lymphoid differentiation programs. Now, in this issue of JEM, Ciucci et al. (2021. J. Exp. Med. demonstrate that this relationship is "central" to the generation of T cell memory.
#1Chuan Li (University of Connecticut)H-Index: 34
#2Yee Peng Phoon (Cleveland Clinic)H-Index: 2
Last. Brian R. Gastman (Cleveland Clinic)H-Index: 36
view all 22 authors...
Immune checkpoint inhibitor (ICI) therapy continues to revolutionize melanoma treatment, but only a subset of patients respond. Major efforts are underway to develop minimally invasive predictive assays of ICI response. Using single-cell transcriptomics, we discovered a unique CD8 T cell blood/tumor-shared subpopulation in melanoma patients with high levels of oxidative phosphorylation (OXPHOS), the ectonucleotidases CD38 and CD39, and both exhaustion and cytotoxicity markers. We called this pop...
#1Claire Drurey (University of Glasgow)H-Index: 8
#2Håvard T. Lindholm (NTNU: Norwegian University of Science and Technology)H-Index: 3
Last. Menno J. Oudhoff (NTNU: Norwegian University of Science and Technology)H-Index: 13
view all 11 authors...
Helminth parasites are adept manipulators of the immune system, using multiple strategies to evade the host type 2 response. In the intestinal niche, the epithelium is crucial for initiating type 2 immunity via tuft cells, which together with goblet cells expand dramatically in response to the type 2 cytokines IL-4 and IL-13. However, it is not known whether helminths modulate these epithelial cell populations. In vitro, using small intestinal organoids, we found that excretory/secretory product...
#1Maximilien Evrard (University of Melbourne)H-Index: 16
#2Erica Wynne-Jones (University of Melbourne)H-Index: 3
Last. Sapna Devi (University of Melbourne)H-Index: 13
view all 18 authors...
Tissue-resident memory T (TRM) cells provide long-lasting immune protection. One of the key events controlling TRM cell development is the local retention of TRM cell precursors coupled to downregulation of molecules necessary for tissue exit. Sphingosine-1-phosphate receptor 5 (S1PR5) is a migratory receptor with an uncharted function in T cells. Here, we show that S1PR5 plays a critical role in T cell infiltration and emigration from peripheral organs, as well as being specifically downregulat...
#1Victoria M Hallisey (NYU: New York University)
#2Susan R. Schwab (NYU: New York University)H-Index: 22
In this elegant study, Evrard et al. (2021. J. Exp. Med. find that sphingosine 1-phosphate receptor 5 (S1PR5) powerfully impairs tissue-resident memory T cell (TRM) formation, and that tissue-derived TGF-β limits S1pr5 expression by infiltrating T cells.
#1Li WangH-Index: 8
Last. Hao Wu (Boston Children's Hospital)H-Index: 100
view all 3 authors...
Inflammasome proteins play an important role in many diseases of high unmet need, making them attractive drug targets. However, drug discovery for inflammasome proteins has been challenging in part due to the difficulty in solving high-resolution structures using cryo-EM or crystallography. Recent advances in the structural biology of NLRP3 and NLRP1 have provided the first set of data that proves a promise for structure-based drug design for this important family of targets.
#1Tianyang Mao (Yale University)H-Index: 20
#2Benjamin Israelow (Yale University)H-Index: 21
Last. Melissa M. Linehan (Yale University)H-Index: 12
view all 16 authors...
As SARS-CoV-2 continues to cause morbidity and mortality around the world, there is an urgent need for the development of effective medical countermeasures. Here, we assessed the antiviral capacity of a minimal RIG-I agonist, stem-loop RNA 14 (SLR14), in viral control, disease prevention, post-infection therapy, and cross-variant protection in mouse models of SARS-CoV-2 infection. A single dose of SLR14 prevented viral infection in the lower respiratory tract and development of severe disease in...
#1Hemraj B. Dodiya (UC: University of Chicago)H-Index: 19
#2Holly L. Lutz (UCSD: University of California, San Diego)H-Index: 12
Last. Sangram S. Sisodia (UC: University of Chicago)H-Index: 93
view all 18 authors...
We previously demonstrated that lifelong antibiotic (ABX) perturbations of the gut microbiome in male APPPS1-21 mice lead to reductions in amyloid β (Aβ) plaque pathology and altered phenotypes of plaque-associated microglia. Here, we show that a short, 7-d treatment of preweaned male mice with high-dose ABX is associated with reductions of Aβ amyloidosis, plaque-localized microglia morphologies, and Aβ-associated degenerative changes at 9 wk of age in male mice only. More importantly, fecal mic...
#1Bassem Khalil (AU: Atlantic University)H-Index: 1
#2Roberto Sanchez (MSSM: Icahn School of Medicine at Mount Sinai)H-Index: 34
Last. Julio A. Aguirre-GhisoH-Index: 45
view all 15 authors...
We describe the discovery of an agonist of the nuclear receptor NR2F1 that specifically activates dormancy programs in malignant cells. The agonist led to a self-regulated increase in NR2F1 mRNA and protein and downstream transcription of a novel dormancy program. This program led to growth arrest of an HNSCC PDX line, human cell lines, and patient-derived organoids in 3D cultures and in vivo. This effect was lost when NR2F1 was knocked out by CRISPR-Cas9. RNA sequencing revealed that agonist tr...
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