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

Autor: Satya P. Singh, Tej Pratap Singh, Hsinyi Tsang, Juraj Kabat, Joshua M. Farber, Lily Koo, Hongwei H. Zhang, Chang Hoon Lee
Rok vydání: 2018
Předmět:
CCAAT-Enhancer-Binding Protein-delta
0301 basic medicine
Chemokine
Mouse
Lymphocyte
Gene Expression
Cell Communication
Immunology and Inflammation
0302 clinical medicine
Cell Movement
Biology (General)
Cells
Cultured
biology
General Neuroscience
General Medicine
Flow Cytometry
Fucosyltransferases
Extravasation
Cell biology
medicine.anatomical_structure
Medicine
medicine.symptom
Selectin
Research Article
Human
Blood vessel
Receptors
CCR6
beta-Galactoside alpha-2
3-Sialyltransferase
QH301-705.5
Receptors
CCR2
Science
T cell
Inflammation
Mucosal associated invariant T cell
Mucosal-Associated Invariant T Cells
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
transcription factors
medicine
Animals
Humans
General Immunology and Microbiology
chemokine
Endothelial Cells
Sialyltransferases
Mice
Inbred C57BL
030104 developmental biology
inflammation
biology.protein
extravasation
030215 immunology
Zdroj: eLife
eLife, Vol 7 (2018)
ISSN: 2050-084X
Popis: 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.
eLife digest Lymphocytes are a type of cell found in the blood that can detect and fight infections: in particular, some of them can leave the bloodstream to enter infected or inflamed tissues. To do so, these lymphocytes use proteins on their surface to roll along the inside wall of the blood vessel; then they stick to this wall and finally they pass through it. For some types of lymphocytes the details of this mechanism – such as precisely which surface proteins are necessary – remain unclear. Here, Lee et al. collect human lymphocytes from the blood of healthy donors, and they identify a subgroup of lymphocytes, called MAIT cells, that are particularly good at moving from blood to infected or inflamed tissues, and further experiments reveal the types of surface proteins that help them do so. Some of these proteins, for example selectin ligands, are important so the MAIT cell can roll on the wall of the blood vessel. Others, like CCR6, are essential for the cell to stop rolling and stick to the wall. Lee et al. also identify C/EBPδ, a regulatory protein inside the MAIT cell that controls how these other two types of proteins are produced. Finally, Lee et al. show that additional proteins, such as CCR2, are necessary for the lymphocyte to cross the vessel wall. The proteins that help lymphocytes move from blood to tissues represent important targets to fight diseases. For example, blocking these proteins could prevent lymphocytes from invading and damaging healthy tissues, which happens in autoimmune diseases like multiple sclerosis. Alternatively, manipulating these proteins could help to engineer lymphocytes that can invade and kill tumor tissues in cancers.
Databáze: OpenAIRE
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