title: Self-recognition of the endothelium enables regulatory T-cell trafficking and defines the kinetics of immune regulation.
abstract: Localization of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells to lymphoid and non-lymphoid tissue is instrumental for the effective control of immune responses. Compared with conventional T cells, Treg cells constitute a minute fraction of the T-cell repertoire. Despite this numeric disadvantage, Tregs efficiently migrate to sites of immune responses reaching an optimal number for the regulation of T effector (Teff) cells. The array and levels of adhesion and chemokine receptor expression by Tregs do not explain their powerful migratory capacity. Here we show that recognition of self-antigens expressed by endothelial cells in target tissue is instrumental for efficient Treg recruitment in vivo. This event relies upon IFN-γ-mediated induction of MHC-class-II molecule expression by the endothelium and requires optimal PI3K p110δ activation by the T-cell receptor. We also show that, once in the tissue, Tregs inhibit Teff recruitment, further enabling a Teff:Treg ratio optimal for regulation.
authors.affiliation: Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Fu
authors.affiliation: Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Madhav
authors.initials: M
authors.lastname: Kishore
authors.affiliation: Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Beartice
authors.initials: B
authors.lastname: Gittens
authors.affiliation: Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Guosu
authors.initials: G
authors.lastname: Wang
authors.affiliation: Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: David
authors.initials: D
authors.lastname: Coe
authors.affiliation: Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Izabela
authors.initials: I
authors.lastname: Komarowska
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, UK.
authors.forename: Elvira
authors.initials: E
authors.lastname: Infante
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, UK.
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Ridley
authors.affiliation: Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Dianne
authors.initials: D
authors.lastname: Cooper
authors.affiliation: Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Mauro
authors.initials: M
authors.lastname: Perretti
authors.affiliation: Centre for Biochemical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Federica M
authors.initials: FM
authors.lastname: Marelli-Berg
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D004727:Endothelium / Q000276:immunology* / Q000378:metabolism*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
chemical_list: D001324:Autoantigens; D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D000949:Histocompatibility Antigens Class II; D053645:Interleukin-2 Receptor alpha Subunit; D019869:Phosphatidylinositol 3-Kinases