Identification and characterization of T reg-like cells in zebrafish.

Autor: Kasheta M; Program in Molecular Medicine and Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA., Painter CA; Program in Molecular Medicine and Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA., Moore FE; Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA.; Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA.; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA.; Harvard Stem Cell Institute, Cambridge, MA., Lobbardi R; Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA.; Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA.; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA.; Harvard Stem Cell Institute, Cambridge, MA., Bryll A; Program in Molecular Medicine and Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA., Freiman E; Program in Molecular Medicine and Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA., Stachura D; Department of Biological Sciences, California State University, Chico, CA., Rogers AB; Department of Biomedical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA., Houvras Y; Departments of Surgery and Medicine, Weill Cornell Medical College, New York, NY., Langenau DM; Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA.; Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA.; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA.; Harvard Stem Cell Institute, Cambridge, MA., Ceol CJ; Program in Molecular Medicine and Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA craig.ceol@umassmed.edu.
Jazyk: angličtina
Zdroj: The Journal of experimental medicine [J Exp Med] 2017 Dec 04; Vol. 214 (12), pp. 3519-3530. Date of Electronic Publication: 2017 Oct 24.
DOI: 10.1084/jem.20162084
Abstrakt: Regulatory T (T reg) cells are a specialized sublineage of T lymphocytes that suppress autoreactive T cells. Functional studies of T reg cells in vitro have defined multiple suppression mechanisms, and studies of T reg-deficient humans and mice have made clear the important role that these cells play in preventing autoimmunity. However, many questions remain about how T reg cells act in vivo. Specifically, it is not clear which suppression mechanisms are most important, where T reg cells act, and how they get there. To begin to address these issues, we sought to identify T reg cells in zebrafish, a model system that provides unparalleled advantages in live-cell imaging and high-throughput genetic analyses. Using a FOXP3 orthologue as a marker, we identified CD4-enriched, mature T lymphocytes with properties of T reg cells. Zebrafish mutant for foxp3a displayed excess T lymphocytes, splenomegaly, and a profound inflammatory phenotype that was suppressed by genetic ablation of lymphocytes. This study identifies T reg-like cells in zebrafish, providing both a model to study the normal functions of these cells in vivo and mutants to explore the consequences of their loss.
(© 2017 Kasheta et al.)
Databáze: MEDLINE