Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 4005K) PDF+supp data (6731K) PPT slides of all figures Supplemental Material Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Google Scholar Articles by Jenne, C. N. Articles by Chun, J. PubMed PubMed Citation Articles by Jenne, C. N. Articles by Chun, J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB N-NITROSO-N-ETHYLUREA Social Bookmarking                            What's this?

¹ Department of Microbiology and Immunology and ² Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143
³ Ramaciotti Immunization Genomics Laboratory, John Curtin School of Medical Research, Australian National University, Canberra ACT 0200, Australia
⁴ Department of Molecular Biology, Helen L. Dorris Child and Adolescent Neuropsychiatric Disorder Institute, The Scripps Research Institute, La Jolla, CA 92037
⁵ Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104
⁶ Department of Immunology, University of Washington, Seattle, WA 98195

CORRESPONDENCE Jason G. Cyster: Jason.Cyster{at}ucsf.edu OR Lewis L. Lanier: lewis.lanier{at}ucsf.edu OR Jerold Chun: jchun{at}scripps.edu

During a screen for ethylnitrosourea-induced mutations in mice affecting blood natural killer (NK) cells, we identified a strain, designated Duane, in which NK cells were reduced in blood and spleen but increased in lymph nodes (LNs) and bone marrow (BM). The accumulation of NK cells in LNs reflected a decreased ability to exit into lymph. This strain carries a point mutation within Tbx21 (T-bet), which generates a defective protein. Duane NK cells have a 30-fold deficiency in sphingosine-1-phosphate receptor 5 (S1P₅) transcript levels, and S1P₅-deficient mice exhibit an egress defect similar to Duane. Chromatin immunoprecipitation confirms binding of T-bet to the S1pr5 locus. S1P-deficient mice exhibit a more severe NK cell egress block, and the FTY720-sensitive S1P₁ also plays a role in NK cell egress from LNs. S1P₅ is not inhibited by CD69, a property that may facilitate trafficking of activated NK cells to effector sites. Finally, the accumulation of NK cells within BM of S1P-deficient mice was associated with reduced numbers in BM sinusoids, suggesting a role for S1P in BM egress. In summary, these findings identify S1P₅ as a T-bet–induced gene that is required for NK cell egress from LNs and BM.

Abbreviations used: ChIP, chromatin immunoprecipitation; ENU, ethylnitrosourea; HA, hemagglutinin; iNKT, invariant NKT; LCMV, lymphocytic choriomeningitis; S1P, sphingosine-1-phosphate; S1P₁, S1P receptor 1; SNP, single nucleotide polymorphism.

© 2009 Jenne et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS