title: PLZF induces an intravascular surveillance program mediated by long-lived LFA-1-ICAM-1 interactions.
abstract: Innate-like NKT cells conspicuously accumulate within the liver microvasculature of healthy mice, crawling on the luminal side of endothelial cells, but their general recirculation pattern and the mechanism of their intravascular behavior have not been elucidated. Using parabiotic mice, we demonstrated that, despite their intravascular location, most liver NKT cells failed to recirculate. Antibody blocking experiments established that they were retained locally through constitutive LFA-1-intercellular adhesion molecule (ICAM) 1 interactions. This unprecedented lifelong intravascular residence could be induced in conventional CD4 T cells by the sole expression of promyelocytic leukemia zinc finger (PLZF), a transcription factor specifically expressed in the NKT lineage. These findings reveal the unique genetic and biochemical pathway that underlies the innate intravascular surveillance program of NKT cells.
authors.affiliation: Committee on Immunology, Howard Hughes Medical Institute, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Seddon Y
authors.initials: SY
authors.lastname: Thomas
authors.forename: Seth T
authors.initials: ST
authors.lastname: Scanlon
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Griewank
authors.forename: Michael G
authors.initials: MG
authors.lastname: Constantinides
authors.forename: Adam K
authors.initials: AK
authors.lastname: Savage
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Barr
authors.forename: Fanyong
authors.initials: F
authors.lastname: Meng
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
authors.forename: Albert
authors.initials: A
authors.lastname: Bendelac
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D002448:Cell Adhesion; D019070:Cell Lineage; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008099:Liver / Q000098:blood supply*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008833:Microcirculation; D008856:Microscopy, Fluorescence / Q000379:methods; D055611:Natural Killer T-Cells / Q000378:metabolism*; D000075722:Promyelocytic Leukemia Zinc Finger Protein
chemical_list: D051741:Kruppel-Like Transcription Factors; D016169:Lymphocyte Function-Associated Antigen-1; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C513267:Zbtb16 protein, mouse; D018799:Intercellular Adhesion Molecule-1