EBI3 is pivotal for the initiation of experimental autoimmune uveitis

Atsunobu Takeda, Eiichi Hasegawa, Takako Fukuhara, Sayaka Hirakawa, Hisakata Yamada, Yang Yang, Takeru Yoshimura, Toshio Hisatomi, Yuji Oshima, Hiroki Yoshida, Koh Hei Sonoda, Tatsuro Ishibashi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Murine experimental autoimmune uveitis (EAU) is a model for human autoimmune uveitis, whose pathogenesis is caused by both Th1 and Th17cell responses. Epstein-Barr virus-induced gene 3 (EBI3) is a component of the heterodimeric cytokines: interleukin (IL)-27 and IL-35. Although IL-27 was shown to initiate Th1 cell development, it is also recognized as a negative regulator of fully activated CD4+ T cells, including Th17cells. Recently, IL-35 also has also been reported to play immunosuppressive roles in autoimmunity. To investigate the roles of EBI3 in EAU, EBI3-/- mice were immunized with human interphotoreceptor retinoid binding protein peptide 1-20 (IRBP) to induce EAU. We observed that the clinical score in EBI3-/- mice was diminished compared with that in EBI3+/+ mice up to day 22 after immunization, whereas the score in EBI3-/- mice reached the same levels as that of EBI3+/+ mice after day 28. Histological analysis revealed a significant reduction of cellular infiltration into the retina in EBI3-/- mice on day 16. Although Th1 cell responses and IRBP-specific IL-10 production were reduced in EBI3-/- mice, the development of Th17cell responses was unaffected on day 9. On day 21, Th1 cell responses and IRBP-specific IL-10 production was restored to the same levels as that in EBI3+/+ mice, and Th17cell responses significantly increased in EBI3-/- mice. Furthermore, Foxp3 expression in CD4+ T cells was comparable between EBI3+/+ and EBI3-/- mice on days 9 and 21. Therefore, these results indicate that EBI3 may be important in EAU initiation by Th1 cell responses and may suppress EAU by inhibition of both Th1 and Th17cell responses in the late/maintenance phase.

Original languageEnglish
Pages (from-to)107-113
Number of pages7
JournalExperimental Eye Research
Volume125
DOIs
Publication statusPublished - Aug 2014

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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