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A. Amadi-Obi, C.-R. Yu, R. N. Fariss, J. Y. Tsai, M. Campos, C. Egwuagu; Il-27 Induces an Anti-Inflammatory State in Retinal Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2524. doi: https://doi.org/.
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Interleukin-27 (IL-27) is a member of the IL-12 family and is a heterodimeric protein comprised of non-covalently linked subunits, IL12p28 and EBI3. We had previously shown that IL-27 is constitutively expressed in the retina, was upregulated by IFN-g during uveitis and inhibited proliferation of TH17 cells. In this study, we sought to identify resident retinal cells that produce IL-27, determine targets of the IL-27 cytokine secreted in retina and investigate effects of IL-27 secretion by retinal cells on inflammatory cells that mediate uveitis.
For immunolocalization of IL-27 expression, vibratome sections were cut from agarose-embedded normal retina and stained with IL27p28, EBI3, IL27 receptor and F4/80 (microglia cell marker) Abs. To examine effects of IL-27 secretion by retinal cells on inflammatory cells, primary retinal cells were co-cultured with TH1 cells with/without neutralization of IL-27 and analyzed by RTPCR, real-time PCR or intracellular cytokine assay with flow cytometry.
Expression of IL27p28 and EBI3 localizes to ganglion cell and inner nuclear layers of the retina. Both subunits also co-localize with F4/80, suggesting that retinal microglia produce IL-27. On the other hand, IL27p28, but not EBI3, is expressed in photoreceptor outer segment. We further show that IL-27-producing primary retinal cells inhibit proliferation of TH1, in part, through induction of SOCS1, SOCS3 and IL-10.
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