ArticleProceedings of the National Academy of Sciences of the United States of America2018
Paracrine costimulation of IFN-γ signaling by integrins modulates CD8 T cell differentiation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 69 citations in OpenAlex.
- Caspase-11-mediated hyperinflammation impairs CD8+ T cell immunity and viral clearance in severe SARS-CoV-2 infection.JCI insight · 2026Article
- Coordinated post-transcriptional regulation facilitates PD-L1 protein production and tumor immune suppression.Cancer letters · 2026Article
- The dual balance of the cytokine network: key messengers of immune activation and triggers of cytokine storm.Biomarker research · 2026Review
- mRNA-based immunotherapy platform targeting endometrial cancer.Journal of translational medicine · 2025Article
- Radiation regulates the expression of HLA-I in esophageal squamous cell carcinoma through interferon-γ.Scientific reports · 2025Article
- Immunological Control of Herpes Simplex Virus Type 1 Infection: A Non-Thermal Plasma-Based Approach.Viruses · 2025Review
- SLAMF7 (CD319) on activated CD8Cell death and differentiation · 2025Article
- Taming Variability in T-Cell Mechanosensing.Cells · 2025Article
- Aiolos promotes CXCR3 expression on Th1 cells via positive regulation of IFN-γ/STAT1 signaling.JCI insight · 2024Article
- IL-2 delivery to CD8Nature communications · 2024Article
- Nonsignaling extracellular spacer regulates tumor antigen selectivity of CAR T cells.Molecular therapy. Oncology · 2024Article
- Site-specific regulation of Th2 differentiation within lymph node microenvironments.The Journal of experimental medicine · 2024Article
- Zfp36l1 establishes the high-affinity CD8 T-cell response by directly linking TCR affinity to cytokine sensing.European journal of immunology · 2024Article
- CDK4/6 inhibitors induce breast cancer senescence with enhanced anti-tumor immunogenic properties compared with DNA-damaging agents.Molecular oncology · 2024Article
- Single-Cell Profiling Indicates a Proinflammatory Role of Meningeal Ectopic Lymphoid Tissue in Experimental Autoimmune Encephalomyelitis.Neurology(R) neuroimmunology & neuroinflammation · 2024Article
- Interferon-γ couples CD8Nature communications · 2023Article
- Memory T cells possess an innate-like function in local protection from mucosal infection.The Journal of clinical investigation · 2023Article
- IFNγ signaling in cytotoxic T cells restricts anti-tumor responses by inhibiting the maintenance and diversity of intra-tumoral stem-like T cells.Nature communications · 2023Article
- Steroid receptor coactivator-3 inhibition generates breast cancer antitumor immune microenvironment.Breast cancer research : BCR · 2022Article
- Optogenetic-controlled immunotherapeutic designer cells for post-surgical cancer immunotherapy.Nature communications · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The cytokine IFN-γ is a critical regulator of immune system development and function. Almost all leukocytes express the receptor for IFN-γ, yet each cell type elicits a different response to this cytokine. Cell type-specific effects of IFN-γ make it difficult to predict the outcomes of the systemic IFN-γ blockade and limit its clinical application, despite many years of research. To better understand the cell-cell interactions and cofactors that specify IFN-γ functions, we focused on the function of IFN-γ on CD8 T cell differentiation. We demonstrated that during bacterial infection, IFN-γ is a dominant paracrine trigger that skews CD8 T cell differentiation toward memory. This skewing is preferentially driven by contact-dependent T cell-T cell (T-T) interactions and the localized IFN-γ secretion among activated CD8 T cells in a unique splenic microenvironment, and is less sensitive to concurrent IFN-γ production by other immune cell populations such as natural killer (NK) cells. Modulation of CD8 T cell differentiation by IFN-γ relies on a nonconventional IFN-γ outcome that occurs specifically within 24 hours following infection. This is driven by IFN-γ costimulation by integrins at T-T synapses, and leads to synergistic phosphorylation of the proximal STAT1 molecule and accelerated IL-2 receptor down-regulation. This study provides evidence of the importance of context-dependent cytokine signaling and gives another example of how cell clusters and the microenvironment drive unique biology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.