FTY720 attenuates lesional interleukin-17+ cell accumulation in rat experimental autoimmune neuritis

• Published in: Neuropathology and applied neurobiology 2009-10, Vol.35 (5), p.487-495
• Main Authors: Zhang, Z-Y., Zhang, Z., Schluesener, H. J.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Chemotaxis, Leukocyte - physiology; experimental autoimmune neuritis; Fingolimod Hydrochloride; Flow Cytometry; FTY720; helper T lymphocyte; Hematologic and hematopoietic diseases; IL-17; Immunohistochemistry; Immunosuppressive Agents - pharmacology; Interleukin-17 - metabolism; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymph Nodes - cytology; Lymph Nodes - immunology; Lysophospholipids - immunology; Lysophospholipids - metabolism; Male; Medical sciences; Neuritis, Autoimmune, Experimental - immunology; Neuritis, Autoimmune, Experimental - metabolism; Neuritis, Autoimmune, Experimental - pathology; Neurology; Propylene Glycols - pharmacology; Rats; Rats, Inbred Lew; Receptors, Lysosphingolipid - immunology; Receptors, Lysosphingolipid - metabolism; Reverse Transcriptase Polymerase Chain Reaction; S1P; Sciatic Nerve - immunology; Sciatic Nerve - pathology; Signal Transduction - immunology; Sphingosine - analogs & derivatives; Sphingosine - immunology; Sphingosine - metabolism; Sphingosine - pharmacology; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology
• ISSN: 0305-1846; 1365-2990
• DOI: 10.1111/j.1365-2990.2009.01016.x

Aims: 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.