Evaluation of Experimental Autoimmune Uveitis in Mice Treated with FTY720

Evaluation of Experimental Autoimmune Uveitis in Mice Treated with FTY720

Autor Commodaro, Alessandra Goncalves Autor UNIFESP Google Scholar
Peron, Jean Pierre S. Google Scholar
Lopes, Camila Takao Google Scholar
Arslanian, Christina Google Scholar
Belfort, Rubens Junior Autor UNIFESP Google Scholar
Rizzo, Luiz Vicente Google Scholar
Bueno, Valquiria Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Albert Einstein Jewish Inst Educ & Res
Resumo PURPOSE. FTY720 (fingolimod) is an immunomodulatory drug capable of preventing T-cell migration to inflammatory sites by binding to and subsequently downregulating the expression of sphingosine-1 phosphate receptor 1 (S1P(1)) leading in turn to T-cell retention in lymphoid organs. Additional effects of FTY720 by increasing functional activity of regulatory T cells have recently been demonstrated, raising the conversion of conventional T cells into regulatory T cells and affecting the sequestration of regulatory T cells in normal mice. in this study, the action of FTY720 in the ocular autoimmune model in mice was investigated.METHODS. Mice were immunized with 161-180 peptide and pertussis toxin and were treated with 1 mg/kg/d FTY720 by gavage (7-21 days postimmunization [dpi]) or left untreated. Spleen cells, harvested 21 dpi, were cultured and assayed for cytokine production. Draining lymph node, spleen, and eye cells 21 dpi were assayed for quantification of T-cell populations. Disease severity was evaluated by histologic examination of the enucleated eyes at 21 and 49 dpi. in addition, anti-IRBP antibodies were analyzed by ELISA.RESULTS. FTY720 was effective in suppressing the experimental autoimmune uveitis score. Although there was a reduction in the number of eye-infiltrating cells, FTY did not prevent Treg accumulation at this site. FTY720 leads to a significant increase of CD4(+)IFN-gamma(+) and CD4(+)Foxp3(+) cell percentages in lymph nodes, suggesting that this site could be the source of Treg cells found in the eye.CONCLUSIONS. the data showed that treatment in vivo with FTY720 was able to suppress EAU in mice. These results are indicative of the possible therapeutic use of FTY720 in ocular autoimmune processes. (Invest Ophthalmol Vis Sci. 2010;51:2568-2574) DOI:10.1167/iovs.09-4769
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Pan-American Ophthalmological Foundation
FADA-Universidade Federal de São Paulo
Número do financiamento FAPESP: 04/14727-0
Pan-American Ophthalmological Foundation: 2007
Data 2010-05-01
Publicado em Investigative Ophthalmology & Visual Science. Rockville: Assoc Research Vision Ophthalmology Inc, v. 51, n. 5, p. 2568-2574, 2010.
ISSN 0146-0404 (Sherpa/Romeo, fator de impacto)
Editor Assoc Research Vision Ophthalmology Inc
Extensão 2568-2574
Fonte http://dx.doi.org/10.1167/iovs.09-4769
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000277180500038
URI http://repositorio.unifesp.br/handle/11600/32492

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