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Wai Po Chong, Reiko Horai, Phyllis Silver, Mary Mattapallil, Rachel Caspi; Amelioration Of Th1 And Th17 Mediated EAU By IL27p28. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3393.
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© ARVO (1962-2015); The Authors (2016-present)
Uveitis involves both Th1 and Th17 immune responses. In animal models, each effector type can mediate experimental autoimmune uveitis (EAU) independently of the other. A method that targets both immune responses would therefoer be an attractive therapeutic approach. The p28 subunit of IL-27, IL27p28, was recently reported to be an antagonist of gp130, which is required for IL-6 and IL-27 signaling. Since IL-6 and IL 27 are important in promoting Th17 and Th1 responses, respectively, we examined the ability of IL27p28 to modulate Th1 and Th17 induced EAU.
The open reading frame of mouse IL27p28 was cloned into an expression vector, pCDNA3.1. Th1 or Th17 EAUs were induced in B10.RIII mice by adoptive transfer of Th1 or Th17 polarized IRBP161-180 TCR transgenic T cells. On the day of adoptive transfer, mice received a hydrodynamic injection of the p28 plasmid to induce in vivo IL27p28 expression. The vector without the IL27p28 insert was also injected as a control. Disease severity was monitored by funduscopy.
After injection of IL27p28 expression plasmid into naïve mice, IL27p28 was detected in the serum for > 7 days after a single hydrodynamic injection of 20 µg plasmid. Adoptive transfer of Th17 cells resulted in an earlier onset of EAU (indidence 66% day 4; 100% day 6) then Th1 cells (incidence 0% day 4; 83% day 6). In Th17 EAU, injection of IL27p28 plasmid decreased disease scores from 1.65±0.29 to 1.1±0.29 (p< 0.05). In Th1 EAU, disease scores were reduced from 1.48±0.51 to 0.63±0.41 (p< 0.05).
Elevated systemic levels of IL27p28 suppress both Th1 and Th17 EAU by inhibiting the pathogenicity of polarized retina-specific effector T cells. This may suggest the usefulness of IL27p28 augmentation in established disease.
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