FTY720 attenuates lesional interleukin-17(+) cell accumulation in rat experimental autoimmune neuritis.
OBJECTIVE
Experimental autoimmune neuritis (EAN) is a well-known animal model of human demyelinating polyneuropathies. Here we have studied the spatiotemporal accumulation of interleukin (IL)-17(+) cells in sciatic nerves of EAN rats and effects of FTY720, an agonist of sphingosine-1-phosphate (S1P) receptors.


METHODS
In this study, we examined the spatiotemporal expression of IL-17 using immunohistochemistry and RT-PCR, and analysed the IL-17(+) cell proportion in blood and lymph nodes using flow cytometry.


RESULTS
In sciatic nerves of EAN rats, IL-17(+) cells were mainly found to concentrate around blood vessels and IL-17(+) cell accumulation was temporally correlated with severity of neurological signs. FTY720, which has been shown to reduce severity of EAN, attenuated accumulation of IL-17(+) cells in sciatic nerves, decreased IL-17(+) cell proportion in peripheral blood, but increased IL-17(+) cell proportion in lymph nodes, suggesting the involvement of S1P signal pathway in regulating IL-17(+) cell trafficking.


CONCLUSIONS
our data are consistent with the possibility that IL-17(+) cells might contribute to the pathogenesis of EAN and the S1P signal pathway may be involved in the in vivo trafficking of IL-17(+) cells.
Zhang
Z-Y
ZY
Institute of Brain Research, University of Tuebingen, Tuebingen, Germany.
Zhang
Z
Z
Schluesener
H J
HJ
D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D000068876:Fingolimod Hydrochloride; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020381:Interleukin-17 / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008246:Lysophospholipids / Q000276:immunology / Q000378:metabolism; D008297:Male; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011409:Propylene Glycols / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D049349:Receptors, Lysosphingolipid / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D007166:Immunosuppressive Agents; D020381:Interleukin-17; D008246:Lysophospholipids; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine