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J Exp Med. 2009 Oct 26;206(11):2469-81. doi: 10.1084/jem.20090525. Epub 2009 Oct 6.

T-bet-dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow.

Author information

1
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.

Abstract

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.

PMID:
19808259
PMCID:
PMC2768857
DOI:
10.1084/jem.20090525
[Indexed for MEDLINE]
Free PMC Article

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