In one paragraphArticle in The Journal of experimental medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
2 · The registryThe trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
3 · Its place in the literatureWho cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
24 authors.
Dominic P GolecLaboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0002-2741-3302 Pedro H Gazzinelli-Guimaraes *Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Science, George Washington University, Washington, DC, USA.ORCID 0000-0003-4932-2206 Daniel Chauss *Immunoregulation Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0002-8343-0860 Kang Yu *Lymphocyte Cell Biology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0009-0003-0893-9397 Hiroyuki Nagashima *Lymphocyte Cell Biology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0001-8405-6746 Anthony C CruzLymphocyte Cell Biology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0009-0003-3799-2103 Tom HillNational Institute of Allergy and Infectious Diseases Collaborative Bioinformatics Resource, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0002-4661-6391 Sundar GanesanResearch Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0003-1132-2016 Jennifer L CannonsLaboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0003-4121-5668 Jillian K PerryLaboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0009-0003-8617-8693 Luis NiveloDepartment of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, USA.ORCID 0000-0002-4943-1827 Ilin JoshiLaboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0003-3861-625X Nicolas PereiraLaboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0003-3654-4029 Fabrício Marcus Silva OliveiraDepartment of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Science, George Washington University, Washington, DC, USA.ORCID 0000-0001-9963-1758 Yufan ZhengLaboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0002-4827-6191 Makheni Jean PierreLaboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0001-7981-6050 Kirk M DrueyLaboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0002-5834-6501 Justin B LackNational Institute of Allergy and Infectious Diseases Collaborative Bioinformatics Resource, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0003-0584-4010 Eric V DangLaboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0002-2389-6167 Thomas B NutmanLaboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0001-6887-4941 Alejandro V VillarinoDepartment of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, USA.ORCID 0000-0001-8068-2176 John J O'SheaLymphocyte Cell Biology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0002-6456-9752 Behdad AfzaliImmunoregulation Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0003-2968-1156 Pamela L SchwartzbergLaboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA.ORCID 0000-0001-6318-9187 Funding
National Institute of Allergy and Infectious DiseasesNIAMS NIH HHSNIDDK NIH HHSNIH HHSUniversity of Miami PG013596University of Miami, Sylvester Comprehensive Cancer Center PG012707
6 · The paper itselfAbstract
While inputs regulating CD4+ T helper (Th) cell differentiation are well defined, the integration of downstream signaling with transcriptional and epigenetic programs that define Th lineage identity remains incompletely resolved. PI3K signaling is a critical regulator of T cell function; activating mutations affecting PI3Kδ result in an immunodeficiency with multiple T cell defects. Using mice expressing activated PI3Kδ, we found aberrant expression of proinflammatory Th1 signature genes under Th2-inducing conditions, both in vivo and in vitro. This dysregulation was driven by a PI3Kδ-IL-2-Foxo1 signaling amplification loop, fueling Foxo1 inactivation, loss of Th2 lineage restriction, and extensive epigenetic reprogramming. Surprisingly, ablation of Fasl, a Foxo1-repressed gene, normalized both Th2 differentiation and TCR signaling. BioID and imaging revealed Fas interactions with TCR signaling components, which were supported by Fas-mediated potentiation of TCR signaling that could occur in the absence of FADD. Our results highlight Fas-FasL signaling as a critical intermediate in phenotypes driven by activated PI3Kδ, thereby linking two key pathways of immune dysregulation.
Indexed as
CD4-Positive T-LymphocytesCell DifferentiationClass I Phosphatidylinositol 3-KinasesFas Ligand ProteinForkhead Box Protein O1Signal TransductionAnimalsInterleukin-2MiceTh2 CellsClass I Phosphatidylinositol 3-KinasesFas Ligand ProteinFasl protein, mouseForkhead Box Protein O1Foxo1 protein, mouseInterleukin-2Pik3cd protein, mouse
Identifiers
PMID41718717
PMCPMC12922663
What OpenQuestion holds
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LicenceCC BY
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