C/EBPδ drives interactions between human MAIT cells and endothelial cells that are important for extravasation

Many mediators and regulators of extravasation by bona fide human memory-phenotype T cells remain undefined. Mucosal-associated invariant T (MAIT) cells are innate-like, antibacterial cells that we found excelled at crossing inflamed endothelium. They displayed abundant selectin ligands, with high expression of FUT7 and ST3GAL4, and expressed CCR6, CCR5, and CCR2, which played non-redundant roles in trafficking on activated endothelial cells. MAIT cells selectively expressed CCAAT/enhancer-binding protein delta (C/EBPδ). Knockdown of C/EBPδ diminished expression of FUT7, ST3GAL4 and CCR6, decreasing MAIT cell rolling and arrest, and consequently the cells’ ability to cross an endothelial monolayer in vitro and extravasate in mice. Nonetheless, knockdown of C/EBPδ did not affect CCR2, which was important for the step of transendothelial migration. Thus, MAIT cells demonstrate a program for extravasastion that includes, in part, C/EBPδ and C/EBPδ-regulated genes, and that could be used to enhance, or targeted to inhibit T cell recruitment into inflamed tissue.

• Publication year

  2018

• Venue

  eLife

• Publication date

  2018-02-22

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.7554/eLife.32532PMID 29469805PMCID 5869018
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Clostridioides difficile Activates Human Mucosal-Associated Invariant T Cells

  2018cited by this paper
• TNF&agr; and IL‐1&bgr; in the synovial fluid facilitate mucosal‐associated invariant T (MAIT) cell migration

  2017influential reference
• Transcriptional networks specifying homeostatic and inflammatory programs of gene expression in human aortic endothelial cells

  2017influential reference
• Mucosal‐associated invariant T cells in autoimmunity, immune‐mediated diseases and airways disease

  2016cited by this paper
• Human mucosal-associated invariant T cells contribute to antiviral influenza immunity via IL-18–dependent activation

  2016cited by this paper
• Antimicrobial Activity.

  2016cited by this paper
• MAIT cells are activated during human viral infections

  2016cited by this paper
• Distinct activation thresholds of human conventional and innate-like memory T cells.

  2016cited by this paper
• STAT5A Modulates Chemokine Receptor CCR6 Expression and Enhances Pre‐B Cell Growth in a CCL20‐Dependent Manner

  2016cited by this paper
• The Chemokine Receptor CX3CR1 Defines Three Antigen-Experienced CD8 T Cell Subsets with Distinct Roles in Immune Surveillance and Homeostasis.

  2016cited by this paper
• MHC class I‐related molecule, MR1, and mucosal‐associated invariant T cells

  2016influential reference
• Human TRAV1-2-negative MR1-restricted T cells detect S. pyogenes and alternatives to MAIT riboflavin-based antigens

  2016cited by this paper
• Diversity of T Cells Restricted by the MHC Class I-Related Molecule MR1 Facilitates Differential Antigen Recognition.

  2016cited by this paper
• Hallmarks of Tissue-Resident Lymphocytes.

  2016cited by this paper
• Epigenomic Profiling of Human CD4+ T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development.

  2016cited by this paper
• Functions of Smad Transcription Factors in TGF-β1–Induced Selectin Ligand Expression on Murine CD4 Th Cells

  2016cited by this paper
• Diverse Inflammatory Cytokines Induce Selectin Ligand Expression on Murine CD4 T Cells via p38α MAPK

  2015cited by this paper
• Biological roles of CCAAT/Enhancer-binding protein delta during inflammation

  2015cited by this paper
• PLZF Regulates CCR6 and Is Critical for the Acquisition and Maintenance of the Th17 Phenotype in Human Cells

  2015cited by this paper
• Check MAIT

  2014cited by this paper
• Deficiency of the Sialyltransferase St3Gal4 Reduces Ccl5-Mediated Myeloid Cell Recruitment and Arrest: Short Communication

  2014cited by this paper
• PHAGOCYTES , GRANULOCYTES , AND MYELOPOIESIS ST 3 Gal-4 is the primary sialyltransferase regulating the synthesis of E-, P-, and L-selectin ligands on human myeloid leukocytes

  2014influential reference
• International Union of Basic and Clinical Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors

  2014influential reference
• Glycogen synthase kinase-3β-mediated CCAAT/enhancer-binding protein delta phosphorylation in astrocytes promotes migration and activation of microglia/macrophages.

  2014cited by this paper
• VLA-4 blockade promotes differential routes into human CNS involving PSGL-1 rolling of T cells and MCAM-adhesion of TH17 cells

  2014cited by this paper
• Correction to “International Union of Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors”

  2014cited by this paper
• Toll-Like Receptor 8 Agonist and Bacteria Trigger Potent Activation of Innate Immune Cells in Human Liver

  2014cited by this paper
• MAIT Cells Detect and Efficiently Lyse Bacterially-Infected Epithelial Cells

  2013cited by this paper
• Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells

  2013cited by this paper
• CCAAT/enhancer-binding protein δ is a critical mediator of lipopolysaccharide-induced acute lung injury.

  2013cited by this paper
• Recirculating Memory T Cells Are a Unique Subset of CD4+ T Cells with a Distinct Phenotype and Migratory Pattern

  2013cited by this paper
• The Many Faces of C/EBPδ and their Relevance for Inflammation and Cancer

  2013cited by this paper
• The integration of T cell migration, differentiation and function

  2013cited by this paper
• MAIT cells are critical for optimal mucosal immune responses during in vivo pulmonary bacterial infection

  2013cited by this paper
• CD161++CD8+ T cells, including the MAIT cell subset, are specifically activated by IL-12+IL-18 in a TCR-independent manner

  2013cited by this paper
• FBXW7α attenuates inflammatory signalling by downregulating C/EBPδ and its target gene Tlr4

  2013cited by this paper
• Distinct glycosyltransferases synthesize E-selectin ligands in human vs. mouse leukocytes

  2013influential reference
• The Impact of KLF2 Modulation on the Transcriptional Program and Function of CD8 T Cells

  2013influential reference
• Role of Macrophage CCAAT/Enhancer Binding Protein Delta in the Pathogenesis of Rheumatoid Arthritis in Collagen-Induced Arthritic Mice

  2012cited by this paper
• Skin infection generates non-migratory memory CD8+ TRM cells providing global skin immunity

  2012cited by this paper
• Hidden Memories: Frontline Memory T Cells and Early Pathogen Interception

  2012cited by this paper
• MR1 presents microbial vitamin B metabolites to MAIT cells

  2012cited by this paper
• Human MAIT and CD8αα cells develop from a pool of type-17 precommitted CD8+ T cells.

  2012cited by this paper
• Coordinated roles of ST3Gal-VI and ST3Gal-IV sialyltransferases in the synthesis of selectin ligands.

  2012cited by this paper
• CCR2+CCR5+ T Cells Produce Matrix Metalloproteinase-9 and Osteopontin in the Pathogenesis of Multiple Sclerosis

  2012cited by this paper
• CCAAT-enhancer binding protein delta (C/EBPδ) protects against Klebsiella pneumoniae-induced pulmonary infection: potential role for macrophage migration.

  2012cited by this paper
• CCL20 and β-Defensin-2 Induce Arrest of Human Th17 Cells on Inflamed Endothelium In Vitro under Flow Conditions

  2011influential reference
• International Union of Basic and Clinical Pharmacology. LXXXII: Nomenclature and Classification of Hydroxy-carboxylic Acid Receptors (GPR81, GPR109A, and GPR109B)

  2011cited by this paper
• Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17-secreting T cells.

  2011cited by this paper
• Transendothelial migration of lymphocytes mediated by intraendothelial vesicle stores rather than by extracellular chemokine depots

  2011influential reference
• Low-Dose Endotoxin Induces Inflammation by Selectively Removing Nuclear Receptors and Activating CCAAT/Enhancer-Binding Protein δ

  2011cited by this paper
• Difference in Th1 and Th17 Lymphocyte Adhesion to Endothelium

  2011influential reference
• Human Mucosal Associated Invariant T Cells Detect Bacterially Infected Cells

  2010cited by this paper
• Antimicrobial activity of mucosal-associated invariant T cells

  2010cited by this paper
• CCL20 and b-Defensin-2 Induce Arrest of Human Th17 Cells on Inflamed Endothelium In Vitro under Flow Conditions

  2010cited by this paper
• CCR2 Identifies a Stable Population of Human Effector Memory CD4+ T Cells Equipped for Rapid Recall Response

  2010influential reference
• Analysis of CD161 expression on human CD8+ T cells defines a distinct functional subset with tissue-homing properties

  2010cited by this paper
• Role of the transcription factor C/EBPδ in a regulatory circuit that discriminates between transient and persistent Toll-like receptor 4-induced signals

  2009cited by this paper
• Glycosylation in immune cell trafficking

  2009influential reference
• Stepwise Development of MAIT Cells in Mouse and Human

  2009cited by this paper
• Chemokine receptor CX3CR1

  2009cited by this paper
• The chemokine receptor CCR5 plays a key role in the early memory CD8+ T cell response to respiratory virus infections.

  2008cited by this paper
• Sialyltransferase ST3Gal-IV controls CXCR2-mediated firm leukocyte arrest during inflammation

  2008cited by this paper
• Human T Cells That Are Able to Produce IL-17 Express the Chemokine Receptor CCR61

  2008cited by this paper
• Cutting Edge: Local Recall Responses by Memory T Cells Newly Recruited to Peripheral Nonlymphoid Tissues

  2008cited by this paper
• Cells on the run: shear-regulated integrin activation in leukocyte rolling and arrest on endothelial cells.

  2008cited by this paper
• Human interleukin 17–producing cells originate from a CD161+CD4+ T cell precursor

  2008cited by this paper
• SOCS1 Regulates CCR7 Expression and Migration of CD4+ T Cells into Peripheral Tissues1

  2008influential reference
• Surface phenotype and antigenic specificity of human interleukin 17–producing T helper memory cells

  2007cited by this paper
• Getting to the site of inflammation: the leukocyte adhesion cascade updated

  2007cited by this paper
• Complete identification of E-selectin ligands on neutrophils reveals distinct functions of PSGL-1, ESL-1, and CD44.

  2007cited by this paper
• Kruppel-like factor 2 regulates thymocyte and T-cell migration

  2006cited by this paper
• Interaction of GATA-3/T-bet transcription factors regulates expression of sialyl Lewis X homing receptors on Th1/Th2 lymphocytes

  2006influential reference
• α2,3‐Sialyltransferase‐IV is essential for L‐selectin ligand function in inflammation

  2006influential reference
• [Toll-like receptor].

  2005cited by this paper
• Participation of the transcription factor C/EBP6 in the acute-phase regulation of the human gene for complement component C3

  2005cited by this paper
• Adhesive mechanisms governing interferon-producing cell recruitment into lymph nodes

  2005influential reference
• Selectins in T-cell recruitment to non-lymphoid tissues and sites of inflammation

  2004influential reference
• IMGT , the international ImMunoGeneTics information system

  2003cited by this paper
• Sialyltransferase specificity in selectin ligand formation.

  2002influential reference
• CCAAT/enhancer-binding proteins: structure, function and regulation.

  2002cited by this paper
• The chemokine KC, but not monocyte chemoattractant protein-1, triggers monocyte arrest on early atherosclerotic endothelium.

  2001cited by this paper
• Specialized roles of the chemokine receptors CCR1 and CCR5 in the recruitment of monocytes and T(H)1-like/CD45RO(+) T cells.

  2001influential reference
• Shear forces promote lymphocyte migration across vascular endothelium bearing apical chemokines

  2001cited by this paper
• Fuc-Tvii Is Required for T Helper 1 and T Cytotoxic 1 Lymphocyte Selectin Ligand Expression and Recruitment in Inflammation, and Together with Fuc-Tiv Regulates Naive T Cell Trafficking to Lymph Nodes

  2001cited by this paper
• Cutting Edge: Differential Requirements for Stat4 in Expression of Glycosyltransferases Responsible for Selectin Ligand Formation in Th1 Cells1

  2001influential reference
• [gamma][delta] cells: a right time and a right place for a conserved third way of protection.

  2000cited by this paper
• Cd4+ T Cell Subsets during Virus Infection

  2000cited by this paper
• Cutting Edge: C-C Chemokine Receptor 6 Is Essential for Arrest of a Subset of Memory T Cells on Activated Dermal Microvascular Endothelial Cells Under Physiologic Flow Conditions In Vitro

  2000influential reference
• Two subsets of memory T lymphocytes with distinct homing potentials and effector functions

  1999cited by this paper
• Cloning and functional characterization of the 5′-flanking region of the human monocyte chemoattractant protein-1 receptor (CCR2) gene : essential role of 5'-untranslated region in tissue-specific expression

  1999cited by this paper
• Cloning and Functional Characterization of the 5′-Flanking Region of the Human Monocyte Chemoattractant Protein-1 Receptor (CCR2) Gene

  1999cited by this paper
• Alpha(1,3)-fucosyltransferase VII and alpha(2,3)-sialyltransferase IV are up-regulated in activated CD4 T cells and maintained after their differentiation into Th1 and migration into inflammatory sites.

  1999cited by this paper
• α(1,3)-Fucosyltransferase VII and α(2,3)-Sialyltransferase IV Are Up-Regulated in Activated CD4 T Cells and Maintained After Their Differentiation into Th1 and Migration into Inflammatory Sites

  1999cited by this paper
• Differential immobilization and hierarchical involvement of chemokines in monocyte arrest and transmigration on inflamed endothelium in shear flow

  1999cited by this paper
• Two subsets of memory T lymphocytes with distinct homing potentials and effector functions

  1999cited by this paper
• Chemokines and the arrest of lymphocytes rolling under flow conditions.

  1998influential reference
• Interleukin 12 and Interleukin 4 Control T Cell Adhesion to Endothelial Selectins through Opposite Effects on α1,3-fucosyltransferase VII Gene Expression

  1998influential reference
• P- and E-selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into inflamed tissues

  1997cited by this paper
• Interleukin 4 or oncostatin M induces a prolonged increase in P- selectin mRNA and protein in human endothelial cells

  1996cited by this paper

• Development and Functions of MAIT Cells.

  2025cites this paper
• Harnessing the Power of Single-Cell Large Language Models with Parameter Efficient Fine-Tuning using scPEFT

  2025influential citation
• BCG Vaccination at Birth Shapes the TCR Usage and Functional Profile of MR1T Cells at 9 Weeks of Age

  2025cites this paper
• Basic biology and roles of CEBPD in cardiovascular disease

  2025influential citation
• Migration arrest and transendothelial trafficking of human pathogenic-like Th17 cells are mediated by differentially positioned chemokines

  2025cites this paper
• MAIT cell homing in intestinal homeostasis and inflammation

  2025cites this paper
• IL-6 trans-signaling mediates cytokine secretion and barrier dysfunction in hantavirus-infected cells and correlates to severity in HFRS

  2024cites this paper
• Unraveling the phenotypic states of human innate-like T cells: Comparative insights with conventional T cells and mouse models

  2024cites this paper
• Insights into the tissue repair features of MAIT cells

  2024cites this paper
• MAIT cell activation and recruitment in inflammation and tissue damage in acute appendicitis

  2024cites this paper
• MAIT cells and the microbiome

  2023cites this paper
• A conserved transcriptional program for MAIT cells across mammalian evolution

  2023cites this paper
• Unraveling the Phenotypic States of Human innate-like T Cells: Comparative Insights with Conventional T Cells and Mouse Models

  2023cites this paper
• Role of MAIT cells in gastrointestinal tract bacterial infections in humans: more than a gut feeling.

  2023cites this paper
• Chemokine positioning determines mutually exclusive roles for their receptors in extravasation of pathogenic human T cells

  2023cites this paper
• Varicella Zoster Virus infects mucosal associated Invariant T cells

  2023cites this paper
• Transcriptional profiling of human Vδ1 T cells reveals a pathogen-driven adaptive differentiation program

  2022cites this paper
• Systems-level identification of key transcription factors in immune cell specification

  2022cites this paper
• Human lung-resident mucosal-associated invariant T cells are abundant, express antimicrobial proteins, and are cytokine responsive

  2022cites this paper
• MAIT cells in liver inflammation and fibrosis

  2022influential citation
• Biomechanics as driver of aggregation of tethers in adherent membranes.

  2021cites this paper
• Non-Tumor CCAAT/Enhancer-Binding Protein Delta Potentiates Tumor Cell Extravasation and Pancreatic Cancer Metastasis Formation

  2021cites this paper
• Human liver‐derived MAIT cells differ from blood MAIT cells in their metabolism and response to TCR‐independent activation

  2020cites this paper
• MAIT Cell Development and Functions: the Microbial Connection.

  2020cites this paper
• Coexistence of long and short DNA constructs within adhesion plaques

  2020cites this paper
• MAIT Cells in Health and Disease.

  2020cites this paper
• A Flow Chamber Assay for Studying MAIT Cell Trafficking.

  2020cites this paper
• Neutrophils suppress mucosal‐associated invariant T cells in humans

  2020cites this paper
• MAIT cell development in mice and humans.

  2020cites this paper
• BigMPI4py: Python module for parallelization of Big Data objects

  2019cites this paper
• A divergent transcriptional landscape underpins the development and functional branching of MAIT cells

  2019cites this paper
• The biology and functional importance of MAIT cells

  2019cites this paper
• Tumor-infiltrating mucosal-associated invariant T (MAIT) cells retain expression of cytotoxic effector molecules

  2019cites this paper
• Differences in the molecular signatures of mucosal-associated invariant T cells and conventional T cells

  2019cites this paper
• Regulatory T cells and mucosal-associated invariant T cells in colon adenocarcinomas; Phenotype and function

  2019cites this paper
• A common transcriptomic program acquired in the thymus defines tissue residency of MAIT and NKT subsets

  2018influential citation