FTY720 Blocks Egress of T Cells in Part by Abrogation of Their Adhesion on the Lymph Node Sinus

Cited 27 time in webofscience Cited 0 time in scopus
  • Hit : 386
  • Download : 0
Egress of lymphocytes from lymphoid tissues is a complex process in which G alpha i-mediated signals play a decisive role. We show here that although FTY720, an agonist of the sphingosine 1-phosphate (S1P)(1) receptor, induces S1P(1) receptor internalization sufficiently in the presence or absence of G alpha i2 or G alpha i3, the drug blocks egress of wild-type (WT) and G alpha i3-deficent T cells, but not G alpha i2-deficient T cells, in both WT and G alpha i2-deficient hosts. Intravital imaging of lymph nodes revealed that all three groups of T cells approached and engaged cortical sinusoids similarly in the presence or absence of FTY720. The cells also entered and departed the sinus at an almost identical frequency in the absence of the drug. However, after engagement of the sinus, most WT and G alpha i3-deficient T cells retracted and migrated back into the parenchyma in FTY720-treated animals, due to a failure of the cells to establish adhesion on the sinus, whereas G alpha i2-deficient T cells adhered firmly on the sinus, which prevented their retraction, facilitating their transmigration of the lymphatic endothelial barrier. These data confirm egress of G alpha i2(-/-) T cells independent of S1P-mediated chemotaxis and failure of FTY720 to close lymphatic stromal channels and argue for the first time, to our knowledge, that FTY720 induces lymphopenia in part by impairing T cell adhesion to the sinus in a manner dependent on G alpha i2. The Journal of Immunology, 2011, 187: 2244-2251.
Publisher
AMER ASSOC IMMUNOLOGISTS
Issue Date
2011-09
Language
English
Article Type
Article
Keywords

SPHINGOSINE 1-PHOSPHATE RECEPTOR-1; TRANSENDOTHELIAL MIGRATION; IMMUNOSUPPRESSANT FTY720; ALPHA-I; MICE; AGONISTS; PROTEIN; S1P(1); ENTRY; RECIRCULATION

Citation

JOURNAL OF IMMUNOLOGY, v.187, no.5, pp.2244 - 2251

ISSN
0022-1767
DOI
10.4049/jimmunol.1100670
URI
http://hdl.handle.net/10203/97985
Appears in Collection
NT-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 27 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0