ArticleThe Journal of experimental medicine2021
Niche-specific MHC II and PD-L1 regulate CD4+CD8αα+ intraepithelial lymphocyte differentiation.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Intestinal Epithelial MHC-II at the Interface of Microbiota, Immunity, and Inflammation.International journal of molecular sciences · 2026Review
- Oral natural extracellular vesicles for biomedical applications: Advances and clinical perspectives.Journal of advanced research · 2026Review
- Fine tuning of TCR signaling via CD8αβ and PD-1 and the fate of autoreactive thymocytes during negative selection.ImmunoHorizons · 2026Article
- CRISPR/Cas9-mediated B2m knockout paves the way for allogeneic basal cell transplantation.Respiratory research · 2026Article
- Systems mapping of intra-donor, cross-tissue T cell clonal expansion and tissue adaptation in the gut-liver-blood axis.Cell reports · 2026Article
- A novel CD112-derived peptide targeting gut-primed neutrophils to attenuate deadly hepatic injury.Molecular medicine (Cambridge, Mass.) · 2026Article
- KMT2D coordinates antiviral CD4Cell reports · 2025Article
- Fiber- and acetate-mediated modulation of MHC-II expression on intestinal epithelium protects from Clostridioides difficile infection.Cell host & microbe · 2025Article
- Role of microRNAs in immunoregulatory functions of epithelial cells.BMC immunology · 2024Review
- Intraepithelial Lymphocytes of the Intestine.Annual review of immunology · 2024Review
- Pathways and mechanisms of CD4Trends in immunology · 2024Review
- Extracellular CIRP induces CD4CD8αα intraepithelial lymphocyte cytotoxicity in sepsis.Molecular medicine (Cambridge, Mass.) · 2024Article
- Intestinal Mucosal Immune Barrier: A Powerful Firewall Against Severe Acute Pancreatitis-Associated Acute Lung Injury via the Gut-Lung Axis.Journal of inflammation research · 2024Review
- Segmented filamentous bacteria-induced epithelial MHCII regulates cognate CD4+ IELs and epithelial turnover.The Journal of experimental medicine · 2024Article
- Edible exosome-like nanoparticles from portulaca oleracea L mitigate DSS-induced colitis via facilitating double-positive CD4Journal of nanobiotechnology · 2023Article
- Downregulation of chemokine receptor 9 facilitates CD4Nature communications · 2023Article
- Runx3d controls the abundance and functional differentiation of CD4Cell death discovery · 2023Article
- Identification of IL-27 as a novel regulator of major histocompatibility complex class I and class II expression, antigen presentation, and processing in intestinal epithelial cells.Frontiers in immunology · 2023Article
- Cytotoxic CD4 T cells in the mucosa and in cancer.Frontiers in immunology · 2023Review
- The homeostatic γc cytokines IL-7 and IL-15 suppress the induction of CD4Cellular & molecular immunology · 2022Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Conventional CD4+ T cells are differentiated into CD4+CD8αα+ intraepithelial lymphocytes (IELs) in the intestine; however, the roles of intestinal epithelial cells (IECs) are poorly understood. Here, we showed that IECs expressed MHC class II (MHC II) and programmed death-ligand 1 (PD-L1) induced by the microbiota and IFN-γ in the distal part of the small intestine, where CD4+ T cells were transformed into CD4+CD8αα+ IELs. Therefore, IEC-specific deletion of MHC II and PD-L1 hindered the development of CD4+CD8αα+ IELs. Intracellularly, PD-1 signals supported the acquisition of CD8αα by down-regulating the CD4-lineage transcription factor, T helper-inducing POZ/Krüppel-like factor (ThPOK), via the Src homology 2 domain-containing tyrosine phosphatase (SHP) pathway. Our results demonstrate that noncanonical antigen presentation with cosignals from IECs constitutes niche adaptation signals to develop tissue-resident CD4+CD8αα+ IELs.
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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.